ANTC:  The Antennapedia Complex
(T.C. Kaufman)
location:  3-47.5.
references:  Kaufman, Lewis, and Wakimoto, 1980, Genetics 94:  115-33.
Lewis, Wakimoto, Denell, and Kaufman, 1980, Genetics 95:  393-97.
Denell, Hummels, Wakimoto, and Kaufman, 1981, Dev. Biol. 81:  43-50.
Kaufman, 1983, Time, Space, and Pattern in Embryonic Development, Alan R. Liss, New York, pp.  365-83.
Kaufman and Abbott, 1984, Molecular Aspects of Early Development, Plenum, New York, pp.  189-218.
Wakimoto, Turner, and Kaufman, 1984, Dev. Biol. 102:  147-72.
Regulski, Harding, Kostriken, Karch, Levin, and McGinnis, 1985, Cell 43:  71-80.
Gehring and Hiromi, 1986, Ann. Rev. Genet. 20:  147-73.
Akam, 1987, Development 101:  1-22.
Fechtel, Natzle, Brown, and Fristrom, 1988, Genes 120:  465-74.
Mahaffey and Kaufman, 1988, Developmental Genetics of Higher Organisms: A Primer in Developmental Biology, Macmillan, New York, pp.  329-59.
Kaufman, Seeger, and Olsen, 1990, Genetic Regulatory Hierarchies in Development, Academic Press, New York, pp.  309-62.
phenotype:  The existence of the homeotic ANTC was originally proposed based on the tight linkage of the proboscipedia (pb). Sex combs reduced (Scr) and Antennapedia (Antp) loci. All were found to reside in a set of three doublet bands at the proximal end of section 84 (84A1,2-3,4 and 84B1,2) in the right arm of polytene chromosome 3. Subsequent genetic analyses have shown that two other homeotic loci labial (lab) and Deformed (Dfd) are also members of the complex. The homeotic loci of the ANTC are involved in the specification of segmental identity in the posterior head (gnathocephalic) and anterior thoracic regions of the embryo and adult. Moreover the linear order of the homeotic loci in the complex lab, pb, Dfd, Scr, and Antp corresponds to the anterior posterior order of altered segments (intercalary, mandibular, maxillary, labial, and thoracic) found in animals bearing mutations in each of the resident loci. Specifically Antp transforms posterior T1, all of T2, and the anterior of T3, Scr transforms T1 and labial, Dfd affects the maxillary and mandibular lobes, pb affects the derivatives of the maxillary and labial segments and finally lab functions in the intercalary segment. Taken together the results of mutational analyses indicate that members of the complex are necessary to repress head development in the thorax (Antp) and elicit normal segmental identity in the anterior thorax (Scr) and posterior head (Scr, Dfd, pb, and lab). The ANTC is distinguished from the bithorax complex not only by virtue of the domain of action of its homeotic loci (anterior vs. posterior) but also by the residence of loci which are not homeotic in nature. Two of these fushi tarazu (ftz) and zerkn  ullt (zen) have been shown to affect segment enumeration (ftz) and the formation of dorsal structures (zen) in the early embryo. A third nonhomeotic gene is bicoid (bcd). Mutations in this locus result in female sterility and maternal effect lethality. Eggs laid by bcd females fail to develop normal anterior ends and instead produce mirror image duplications of structures normally produced at the posterior terminus of the embryo. In addition to these genetically defined loci there are several other "genes" which have been found in the ANTC by molecular mapping. The first of these is a cluster of cuticle-protein-related genes which map between the lab and pb loci. Eight small (ca. 1 kb) transcription units make up the cluster and all have sequence similarities to known cuticle protein genes. These "genes" are also apparently regulated by ecdysone in imaginal discs. Deletion of the entire cluster has no apparent effect on the development or cuticle morphology of embryos, larvae, or adults. The second molecularly identified "gene" is the Amalgam (Ama) transcription unit. The encoded protein places the gene in the immunoglobulin superfamily and like the cuticle cluster the locus can be deleted from the genome with no discernible effect on the organism.
cytology:  Placed in the 84A1-B2 interval by the inclusion of the complex in Df(3R)Scr and the location of breakpoint associated inactivations of the lab, pb, Dfd, Scr, ftz, and Antp loci.
molecular biology:  The entire complex has been cloned and has been shown to cover 335 kb of genomic DNA. The most distal transcription unit is Antp which covers the distal-most 100 kb of the complex and is made up of eight exons. Proximally the next 75 kb contain the Scr and ftz loci. The distal 50 kb of this interval house sequences necessary for Scr expression as well as the two exons of the ftz locus and its associated regulatory elements. The proximal 25-kb contain the three identified exons of the Scr transcription unit. The five exons of the Dfd gene are found in the central portion of the next-most-proximal 55-kb interval. The Dfd transcription unit covers only 11 kb of this region and it is likely that one or both of the 20-kb intervals flanking the gene are the location of cis-acting regulatory elements for the locus. The next 25-kb interval contains four of the nonhomeotic transcription units which help distinguish the ANTC and BXC. The distal most is Ama, next bcd, and finally zen and z2. The z2, zen, and Ama transcription units are all relatively small (1-2 kb) and comprise two exons each. The bcd gene is somewhat larger (3.6 kb) and is made up of four exons. Immediately proximal to the z2 transcription unit (ca. 1 kb from its 3   end) is the 5   end of pb; the latter gene extends over the next 35 kb of genomic DNA and contains nine exons. The next 25 kb of the complex contain the cuticle cluster and its eight identified transcription units. The final 25 kb are the residence of the lab gene which is made up of three exons.
Despite the nonhomeotic nature of three of the smaller transcription units (zen, bcd, and ftz) resident in the complex, these loci are tied to the larger homeotic genes of the region by the nature of their protein products. All five of the large homeotics (Antp, Scr, Dfd, pb, and lab) and the three small genes have a homeobox motif and their protein products are found in the nuclei of the cells in which they are expressed. Thus eight of the genes in the ANTC encode regulatory proteins which act as transcription factors. The z2 gene also contains a homeobox; however, the biological significance of the gene is not known as deletions of this transcription unit have no discernible effect. The cuticle-like genes and Ama do not contain a homeobox.
The reasons for the clustering of these developmentally significant loci of similar function is not known. The existence of common or overlapping regulatory elements, the need to insulate regulatory sequences from position effect and the possibility of higher order chromatin structures for proper expression have all been proposed. Whatever the reason, the homeotic complex structure has a long evolutionary standing. Similar clusters are found in vertebrates, an observation consistent with a very early origin of these genes, likely predating the separation of protostomes and deuterostomes.

 Ama:  Amalgam 
location:  1-{47.5}.
origin:  Isolated as an unidentified third transcription unit in a 50 kb region known to harbor bcd and zen.
references:  Seeger, Haffley, and Kaufman, 1988, Cell 55:  589-600.
phenotype:  Antibody staining first detects Amalgam in the mesoderm during gastrulation; as neuroblasts delaminate from the ectoderm staining appears in a row of mesectodermal cells along the ventral midline of the extended germ band. Amalgam appears in the first neurons generated from the ganglion-mother cells, but not in the neuroblast precursors of these cells. Neuronal accumulation of Ama gene product increases during CNS development, but appears to be confined to the CNS and initially does not extend to axons exiting the CNS in segmental, intersegmental, or peripheral nerves; with time three rows of PNS-associated cells accumulate Ama protein; staining heavy around spiracle sensory organ and several cephalic sensory structures. Simultaneously there is a complicated temporal and spatial sequence of staining of mesodermal derivatives. Embryonic phenotype of deletion of Ama attributable to simultaneous deletion of zen; no effect of Ama^- detectable.
cytology:  Placed in 84A1 based on its juxtaposition with bcd.
molecular biology:  Sequence of a putatively full-length cDNA clone compared with that of the corresponding genomic region reveals a gene with a 316 bp intron in the 5   untranslated region. Transcription from left to right. Conceptual amino-acid sequence indicates a protein product of 333 amino acids, the first 23 of which have the characteristics of a signal sequence. The sequence contains three internal repeats of approximately 100 amino acids each that exhibit homology to the immunoglobulin or Ig domain of vertebrates; each contains two widely spaced cysteine residues and the show 22-36% identity to one another with greatest identity found around the cysteines. There are two potential N-linked glycosylation sites in the first domain and one in the third. In addition there is a potential C-terminal membrane-attachment domain of amino acids. Comparison with sequences in the data base indicate that the Amalgam sequence is closest to members of the Ig class of proteins that act as cell-adhesion molecules.

Antp^LC:  Antennapedia of Le Calvez
From Le Calvez, 1948, Bull. Biol. France Belg. 82:  97-113.

 Antp:  Antennapedia 
location:  3-47.5.
references:  Denell, 1973, Genetics 75:  279-97.
Struhl, 1981, Nature 292:  635-38.
Garber, Kuroiwa, and Gehring, 1983, EMBO J. 2:  2027-34.
Hafen, Levine, Garber, and Gehring, 1983, EMBO J. 2:  617-23.
Hazelrigg and Kaufman, 1983, Genetics 105:  581-600.
Levine, Hafen, Garber, and Gehring, 1983, EMBO J. 2:  2037-46.
Scott, Weiner, Polisky, Hazelrigg, Pirrotta, Scalenghe, and Kaufman, 1983, Cell 35:  763-76.
Hafen, Levine, and Gehring, 1984, Nature 307:  287-89.
Abbott and Kaufman, 1986, Genetics 114:  919-42.
Carroll, Laymon, McCutcheon, Riley, and Scott, 1986, Cell 47:  113-22.
Frischer, Hagen, and Garber, 1986, Cell 47:  1017-23.
Laughnon, Boulet, Bermingham, Laymon, and Scott, 1986, Mol. Cell Biol. 6:  4676-89.
Martinez-Arias, 1986, EMBO J. 5:  135-41.
Schneuwly, Kuroiwa, Baumgartern, and Gehring, 1986, EMBO J. 5:  733-39.
Wirz, Fessler, and Gehring, 1986, EMBO J. 5:  3327-34.
Jorgensen and Garber, 1987, Genes Dev. 1:  544-55.
Schneuwly, Klemenz, and Gehring, 1987, Nature 325:  816-18.
Schneuwly, Klemenz, and Gehring, 1987, EMBO J. 6:  201-06.
Bermingham and Scott, 1988, EMBO J.  7:  3211-22.
Boulet and Scott, 1988, Genes Dev. 2:  1600-14.
Gibson and Gehring, 1988, Development 102:  657-75.
Muller, Affolter, Leupin, Otting, Wuthrich, and Gehring, 1988, EMBO J. 7:  4299-304.
Otting, Gottfried, Qian, Muller, Affolter, Gehring, and Wuthrich, 1988, EMBO J. 7:  4305-09.
Perkins, Dailey, and Tjian, 1988, Genes Dev. 2:  1615-26.
Stroeher, Gaiser, and Garber, 1988, Mol. Cell Biol. 8:  4667-75.
Bermingham, Martinez-Arias, Petitt, and Scott, 1990, Development 109:  553-66.
phenotype:  Null loss-of-function alleles result in embryonic lethality. Animals succumb at the end of embryogenesis and show homeotic transformations in the larval cuticle of the first, second, and third thoracic segments. Specifically the cuticle derived from parasegments 4 and 5 are transformed to a more anterior identity such that the posterior of the first thorax produces fragments of mouth hook material on its dorsal surface presumably owing to a new posterior labial identity, whereas the anterior of the second thorax resembles the first thorax. The anterior of the third thoracic segment is weakly transformed toward a T1-like identity. The posterior of T2 is presumably T1 like as there are no gnathal structures seen in this compartment. There are also partial loss-of-function mutations which allow survival into the larval, pupal, and adult stages. Those that allow adult survival produce animals in which the anterior of the dorsal mesothorax shows a transformation to prothorax. There are no other apparent defects associated with these lesions. Those "leaky" mutants which die in the pupal and larval stages show similar parasegmental transformations as the null alleles, except that only the parasegment 4 to 3 homeosis is generally apparent. Animals which survive to the pupal stage fail to evert their anterior spiracles resulting in a blunt appearance of the anterior pupa. This same phenotype is seen in genotypes which survive to the adult stage. These partial mutants in many cases are associated with chromosome rearrangements notably deletions which approach the locus from its distal end. Moreover these mutations have been shown to complement fully other seemingly null mutations. Subsequent molecular analyses have shown that these results are accounted for by the presence of two promotors, one, P1, distal to the other, P2. The partial mutants affect the ability of the P1 promotor to initiate transcription, while the complementing lesions inactivate P2. Null mutants affect the transcription unit and protein encoding portion of the gene which is common to both promotors (see below).
X-ray induced somatic clones of Antp^- cells demonstrate that the locus is required in the adult for the proper development of the dorsal pro and mesothorax, and legs. The former is reduced in size presumably reflecting an anteriorward transformation while the latter are transformed to antennae. Thus Antp^+ function is required in the embryo and adult in parasegments 4 and 5 to prevent more anterior segmental identities, specifically those normally found in the anterior thorax and head.
The Antp locus was initially recognized by virtue of several striking dominant gain-of-function alleles. Thirteen of these transform the antenna of the adult into a mesothoracic leg (Antp^49, Antp^B, Antp^Yu, Antp^Pw, Antp^LC, Antp^R, Antp^Wu, Antp^50, Antp^RM, Antp^73b, Antp^CB, Antp^72j, and Antp^Ns). Three of these also have effects on the orbit of the eye and the vibrissal region of the ventral head (Antp^RM, Antp^72j, and Antp^Ns). There are also two dominant alleles (Antp^Ctx and Antp^W) which transform portions of the head capsule (dorsal and posterior) and the eye to a dorsal mesothoracic identity. In some cases this includes the production of wing tissue in the eye. Finally, a unique dominant Antp^Hu produces bristles on the normally bald propleurae just ventral to the mesothoracic spiricle. This latter phenotype has been interpreted as the production of sternopleural bristles on the propleurae, and thus a T1 to T2 transformation. With the exception of Antp^Ns and Antp^72j all these dominant lesions are associated with recessive lethality and gross chromosome rearrangements. All the breakpoints fall in the interval between the distal and proximal promotors. The dominant gain-of-function phenotype results from the misregulation of the P2 promotor by position affect or by the production of novel transcripts initiated in the newly juxtaposed sequences and spliced to the downstream Antp coding sequences. Both events result in the ectopic accumulation of the Antp protein product in the eye-antennal disc where the normal head repressive function of the gene causes the observed alteration. The recessive lethality associated with these lesions falls into the partially deficient category mentioned above. That is, these lesions show complementation with the P2 specific (Antp^1 and Antp^23) mutations and in general show only strong parasegment 4 Æ parasegment 3 transformations. However, there is a gradient of this affect among the breakpoints. Those closest to P1 and furthest from P2 are the weakest, whereas those close to P2 show the strongest phenotype and earlier lethal phase. This same result is obtained with breakpoint mutations in the P2-to-P1 interval which are not associated with a dominant phenotype. Therefore this interval likely contains sequences necessary for the proper regulation of the P2 promoter.
Three of the dominant gain-of-function lesions (Antp^Hu, Antp^73b, and Antp^Ns) have been reverted. The revertants are either complete nulls, thus obviating the potential for ectopic expression, or are partial mutants; the latter mutants likely remove the potential for ectopic expression by altering the juxtaposed sequences required for abnormal P2 activity.
Both in situ hybridization and immunostaining have been used to determine the spatio-temporal pattern of Antp expression. Both the protein and RNA are strongly accumulated in the ventral nerve cord and more weakly in the epidermis and mesoderm of the embryo. Protein and RNA are first detected during cellular blastoderm in a band of cells in the parasegment 4-6 anlagen. This initial spatial pattern is further elaborated at full germ-band extension. In the ectoderm Antp products are found starting in the region of the first thoracic segment (parasegments 3 and 4) and extending posteriorly to the level of the seventh abdominal segment. In the mesoderm, they are found in parasegments 4-6. During germ band shortening the gene products are accumulated in the CNS from parasegment 4 (posterior T1) through to the posterior end of the ventral nerve cord. In the integument transcripts and protein are mainly restricted to the parasegments 4-5 interval although some weak expression can be seen in parasegments 3. As embryogenesis proceeds, the posterior CNS expression diminishes but is still detectable at the end of embryogenesis. The major accumulation in the CNS at this time is in the neuromeres of parasegments 4 and 5. The mesodermal expression is found in the anterior midgut; quenching of Antp expression is found in the posterior portion of the anterior midgut and has been shown to be dependent on the expression of Ubx. In later stages Antp protein can be detected in the leg, dorsal prothoracic, and wing discs.
alleles:  

allele	origin	discoverer	synonym	type	cytology	
						
Antp^1	X ray	Abbott	Antp^a58	hypomorphic	normal	
Antp^2	X ray	Abbott	Antp^a60	hypomorphic	Df(3R)84B2;84D3	
Antp^3	X ray	Abbott	Antp^a62	null	normal	
Antp^4	X ray	Abbott	Antp^a71	null	normal	
Antp^5	X ray	Abbott	Antp^a74	null	In(3R)84B2;87C	
Antp^6	X ray	Abbott	Antp^a75	hypomorphic	Df(3R)84B2-C6	
Antp^7	EMS	Denell	Antp^d7	null	normal	
Antp^8	DEB	Stephenson	Antp^e8	null	normal	
Antp^9	EMS	Fornili	Antp^f9	hypomorphic	normal	
Antp^10	EMS	Fornili	Antp^f22	null	normal	
Antp^11	EMS	Fornili	Antp^f36	null	normal	
Antp^12	EMS	Fornili	Antp^f40	null	normal	
Antp^13	EMS	Fornili	Antp^f69	null	normal	
Antp^14	X ray	Kaufman	Antp^k4	null	T(2;3)36C-D;	
					84B1-2	
					+ In(3LR)62B;	
					98F	
Antp^15	EMS	Kaufman	Antp^k5	null	normal	
Antp^16	EMS	Matthews	Antp^kml	null	?	
Antp^17	X ray	Lopez	Antp^l1	hypomorphic	T(2;3)25F;84B1-2	
Antp^18	X ray	Lopez	Antp^l2	null	normal	
Antp^19	X ray	Pultz	Antp^p4	null	normal	
Antp^20	EMS	R. Lewis	Antp^r4	hypomorphic	normal	
Antp^21	EMS	R. Lewis	Antp^r10	null	normal	
Antp^22	EMS	R. Lewis	Antp^r17	null	normal	
Antp^23	X ray	Scott	Antp^s1	hypomorphic	normal	
Antp^24	X ray	Scott	Antp^s2	hypomorphic	In(3R)80;84B1-2	
Antp^25	EMS	Wakimoto	Antp^w10	null	normal	
Antp^26	EMS	Wakimoto	Antp^w24	null	normal	
Antp^49	X ray	Piternick	Antp^4703	weak	lesion in 84B1-2	
Antp^50	X ray	Piternick	Antp^4715	strong	extra band distal	
					to 84B1-2	
Antp^59	X ray	Piternick		weak	= Antp^49 ?	
Antp^60	X ray	Piternick		weak	= Antp^50 ?	
Antp^72j	spont	Baker		viable	normal	
Antp^73b	spont	Green		strong	In(3R)84B1-2	
Antp^73b-rv1	spont	Green		Antp^73b revertant		
Antp^73b-rv2	spont	Green		Antp^73b revertant		
Antp^73b-rv5	X ray	Hazelrigg		Antp^73b revertant	T(2;3)57B6-8;	
					84B1-2;97B3	
Antp^73b-rv7	X ray	Hazelrigg		Antp^73b revertant	T(2;3)40;84B1-2	
Antp^73b-rv8	X ray	Hazelrigg		Antp^73b revertant	Dp(3;3)84D5-8;	
					85F5-8	
Antp^73b-rv9	X ray	Hazelrigg		Antp^73b revertant	In(3R)84B1-2;	
					84C5-6	
Antp^B	X ray	Bacon		moderate dominant	In(3R)84B1-2;85E	
Antp^CB	X ray	Black		moderate dominant	In(3R)84B1-2;	
					99F-100A	
Antp^Ctx	X ray	Lewis	Ctx	strong dominant	T(2;3)35B;84B1-2	
Antp^Hu	X ray	Ruch	Hu	moderate dominant	In(3R)84B1-2;	
					84F4;86C7-8	
Antp^Hu-rv1	X ray	Hazelrigg		Antp^Hu revertant	Df(3R)84B1-2;	
					84D6-F4	
Antp^JK	spont	Kennison		recessive		
Antp^LC	Neutron	LeCalvez	Ar;ss^Ar	moderate dominant	In(3R)84A5-6;92A5-6	
Antp^Ns	spont	Gehring	Ns	viable dominant	normal	
Antp^Ns-rv1	X ray	Denell		Antp^Ns revertant	In(3R)81;84B1-2	
Antp^Ns-rv2	g ray	Duncan		Antp^Ns revertant	In(3R)81F;90BC	
Antp^Ns-rv3	g ray	Duncan		Antp^Ns revertant	T(Y;3)Y;84A4-B2	
Antp^Ns-rv6	g ray	Duncan		Antp^Ns revertant	In(3LR)79D1-2;	
					84A4-B2	
Antp^Ns-rv8	g ray	Duncan		Antp^Ns revertant	normal	
Antp^Ns-rv11	X ray	Denell		Antp^Ns revertant	normal	
Antp^Ns-rv13	g ray	Duncan		Antp^Ns revertant	T(2;3)84A4-B2;	
					40-41	
Antp^Ns-rv16	g ray	Duncan		Antp^Ns revertant	Complex	
Antp^Ns-rv18	g ray	Duncan		Antp^Ns revertant	T(Y;3)Y;84A4-B2	
Antp^Ns-rv19	g ray	Duncan		Antp^Ns revertant	T(Y;3)Y;84B1-3	
Antp^Ns-rv25	X ray	Denell		Antp^Ns revertant	In(3R)81;	
					84B1-2;85A	
Antp^Ns-rv70	X ray	Denell		Antp^Ns revertant	normal	
Antp^Ns-rv72	X ray	Denell		Antp^Ns revertant	Df(3R)84B3;84D	
Antp^Ns-rv85	X ray	Denell		Antp^Ns revertant	In(3R)81;84B1-2	
Antp^Ns-rv96	X ray	Denell		Antp^Ns revertant	T(Y;3)Y;84B1-2;94C	
Antp^Ns-rvC1	EMS	Struhl		Antp^Ns revertant	normal	
Antp^Ns-rvC2	EMS	Struhl		Antp^Ns revertant	normal	
Antp^Ns-rvC3	EMS	Struhl		Antp^Ns revertant	normal	
Antp^Ns-rvC4	EMS	Struhl		Antp^Ns revertant	In(3LR)75B;84B1-2	
Antp^Ns-rvC5	EMS	Struhl		Antp^Ns revertant	normal 	
Antp^Ns-rvC6	EMS	Struhl		Antp^Ns revertant	normal	
Antp^Ns-rvC8	EMS	Struhl		Antp^Ns revertant	T(2;3)41;84B1-2	
Antp^Ns-rvC9	EMS	Struhl		Antp^Ns revertant	normal	
Antp^Ns-rvC10	EMS	Struhl		Antp^Ns revertant	T(Y;3)Y;84B1-2	
Antp^Ns-rvC11	EMS	Struhl		Antp^Ns revertant	normal	
Antp^Ns-rvC12	EMS	Struhl		Antp^Ns revertant	normal	
Antp^PW	MDN ^a	Pinchin		strong dominant	In(3LR)71F;84B1-2	
Antp^R	X ray	Rappaport	ss^a	moderate dominant	In(3R)84B1-2;86C	
Antp^RM	X ray	R. Meyer		moderate dominant	In(3R)82E1;84B1-2	
Antp^Scx	spont	Hannah	Scx	weak dominant	normal	
Antp^W	X ray	Wohlwill		moderate dominant	T(3;4)84B1-2;102F	
					+ T(2;3)33E;66C	
Antp^Wu	g ray	Wu		strong dominant	In(3LR)75C;84B1-2	
Antp^Yu	X ray	Yu		strong dominant	T(2;3)22B;83E-F	
					+ T(2;3)38E;98A	

^a

MDN =  methoxy diethylnitrosamine.

cytology:  Placed in 84B1-2 based on Antp’s inclusion in the overlap region between Df(3R)Scr and Df(3R)A41 as well as the commonly held breakpoint of four forward, eleven gain-of-function and eighteen revertant of gain-of-function mutations (see table of alleles).
molecular biology:  The Antp transcription unit lies at the distal end of the ANTC and is transcribed in a distal to proximal (i.e., left to right) direction with respect to the right arm of the third chromosome. The locus has been identified in the DNA through the localization of breakpoints associated with both loss- and gain-of-function mutations. Additionally regulatory portions of the gene have been used to drive the expression of b galactosidase reporter constructs in vivo and these constructs produce spatial patterns of expression similar to those seen for the normal gene. The identified transcription unit is 100 kb long and is made up of eight exons. Exons 1 and 2 are the most distal and are found at the 5   end of RNAs initiated from the P1 promotor mentioned previously. Exon 3 is approximately 60 kb downstream of the P1 5   end and represents the leader sequences unique to transcripts initiated at the P2 promotor. The remaining five exons (E4-E8) are common to transcripts initiated at both P1 and P2. Exon 4 also encodes a leader sequence and the identified open reading frame begins in exon 5, 36 nucleotides downstream of the splice acceptor. The open reading frame continues through exons 6, 7, and 8 ending 240 nucleotides downstream of the splice acceptor of E8. Two polyadenylation sites are used at the downstream end of E8. The first (A1) is ca. 875 nucleotides downstream of the 5   end of the exon; the other (A2) is ca. 2300 nucleotides more proximal. The two promotors coupled with the two adenylation sites result in the production of four size classes of transcript (P1/A1 = 3.2 kb, P1/A2 = 4.6 kb, P2/A1 = 3.4 kb, P2/A2 = 4.8 kb). All of these have been seen on Northern blots. There is no apparent preferential association of promotor with respect to 3   end formation. However, the two promotors do have different spatial patterns of expression. Notably the P1 promotor is seen to be strongly expressed in the anlagen of the dorsal prothoracic disc, a tissue dramatically affected by its deletion. The P2 promotor is more evenly expressed in Antp’s spatial domain (see below), consistent with the defects associated with its inactivation. The 3   end of the transcription unit is ca. 30 kb distal to the 3   end of ftz and 50 kb distal to the identified 5   end of Scr. The distance to the next most distal transcription unit from the P1 5   end is nearly 50 kb. The site of the Antp^Hu breakpoint is in this 50 kb interval.
In addition to the transcript heterogeneity mentioned above, Antp also undergoes alternate splicing among the ORF-containing introns. Specifically exon 6 which encodes thirteen amino acids is found predominantly in embryonic transcripts and less frequently in imaginal disc derived RNAs. Additionally there is an alternate splice at the 3   end of exon 7, resulting in the deletion of four amino acids just upstream of the homeobox motif if the short splice is made. It appears that the long form splice is used preferentially but that all four potential protein forms are made in imaginal discs. The exon-6-less transcripts are rare in embryonic RNA. There is no apparent preferential association of alternate splicing patterns with either of the two promotors. The longest potential protein (E6 + 7L) is 378 amino acids in length, and has a predicted molecular weight of 43 kd. The homeobox motif is encoded in E8 and the opa like repeats in E5.

 bcd:  bicoid 
location:  3-{47.5} (between zen and Ama).
synonym:  mum:  multimorph.
references:  Frohnh  ofer and N  usslein-Vollhard, 1986, Nature (London) 324:  120-25 (fig.).
Fronh  ofer and N  usslein-Volhard, 1987, Genes Dev. 1:  603-14.
phenotype:  Maternal-effect lethal mutations showing defective head and thorax development.  Females homozygous for strong alleles produce embryos in which head and thorax are replaced by duplicated telson, including anal plates, tuft, spiracles, and filzk  orper; however, no pole cells formed at the anterior end.  Deletions and fusions of anterior abdominal segments and occasionally anterior abdominal segments in reversed polarity are also observed.  Strong alleles amorphic based on phenotypic similarities of embryos produced by homozygous and hemizygous females.  Weak alleles result in pattern defects in heads of embryos; lack only labral derivatives (median tooth, dorsal bridge); intermediate weak genotypes produce reduced head but retain normal thoracic development; intermediate strong produce further reduction of head, deletion of second and third and reduction of first thoracic dentical belts; thoracic segments fused.  Partial rescue of embryonic phenotype effected by injection of cytoplasm (5% of volume) from the anterior ends of unfertilized wild-type eggs into the anterior pole of newly fertilized eggs of bcd mothers; injection into ectopic sites stimulates differentiation of anterior structures at site of injection; efficiency proportional to number of bcd^+ alleles carried by cytoplasm donor.  Phenocopies result from leakage of 5% of egg volume from anterior perforation of normal embryos. The distance of the head fold at gastrulation is proportional to the number of bcd^+ alleles in the maternal genotype. bcd mRNA appears as a flattened disc plastered to the anterior extremity of early embryos; by the time of pole cell migration it has become localized to the clear cytoplasm at the periphery, forming a cap over the anterior end of the egg and is distributed in a steeply decreasing gradient such that 90% of the RNA is in the anterior 18% of egg length; by nuclear cycle 14 the RNA begins to disappear and becomes undetectable by midway through cellularization. bcd protein on the other hand forms a shallower gradient in which 57% of protein is in the anterior 18% of egg length, and the gradient doesn’t reach baseline until the posterior 30% of egg length; the gradient forms from two to four hours after oviposition in both fertilized and unfertilized eggs, and except during mitosis is concentrated in nuclei; diffusion postulated to account for the establishment of the protein gradient following translation from anteriorly anchored RNA. Protein levels decrease during cellularization, although some nuclear staining persists until the end of germ-band elongation. bcd transcript first detectable in the ovaries of bcd females; forms a ring around the anterior margin of the developing oocyte in stages 5 and 6; in stages 9 and 10 nurse-cell accumulation observed to be localized toward the periphery of the cyst; by stage 12 the nurse cells have emptied their contents into the oocyte and the bcd transcript appears as an anterior cap (St. Johnston, Driever, Berleth, Richstein, and N  usslein-Volhard, 1989, Development Supplement:  13-19). No evidence of translation of bcd protein during oogenesis. Formation of the bcd gradient is regulated by three maternally active genes exu, sww, and stau; exu appears necessary for nurse cell accumulation; sww is required for anterior localization of bcd mRNA in the oocyte; and stau appears to be involved in RNA localization in the embryo. A defect in any of these functions results in little or no gradient of bcd activity. bcd in turn appears to control the activity of anterior gene activity; specifically the anterior pattern of hb expression is not observed and is replaced by a mirror-image posterior hb stripe in bcd^- embryos (Tautz, 1988, Nature 332:  281-84; Schr  oder, Tautz, Seifertz, and J  ackle, 1988, EMBO J. 7:  2881-87).
alleles:  

allele	origin	synonym	ref ^a	comments	
					
bcd^1	EMS	bcd^085	2, 5	intermediate allele; 2564 C Æ T;	
				184 gln Æ amber	
bcd^2	EMS	bcd^2-13	2, 5	weak allele; 3885 T Æ A;	
				453 leu Æ his	
bcd^3	EMS	bcd^23-16	2	strong allele	
bcd^4	EMS	bcd^33-5	2	strong allele	
bcd^5	EMS	bcd^111	2, 5	weak allele; 2798 C Æ T;	
				262 gln Æ amber	
bcd^6	EMS	bcd^E1	1, 2, 5	strong allele; 2482-2650 deleted	
				+ TA inserted; frameshift Æ 55	
				out-of-frame amino acids replacing 	
				amino acids 156-494, including 	
				homeodomain	
bcd^7	EMS	bcd^E2	1, 2	Strong allele; 260 base-pair deletion	
				overlapping homeodomain	
bcd^8	EMS	bcd^E3	2, 5	intermediate allele; strongly temperature	
				sensitive; 2406 C Æ T; 131 ser Æ leu	
bcd^9	EMS	bcd^E4	2, 5	intermediate allele; 2393 C Æ T;	
				127 leu Æ phe	
bcd^10	EMS	bcd^E5	2, 5	weak allele; 2804 C Æ T;	
				264 gln Æ amber	
bcd^11	EMS	bcd^E6	5	2388-2420 deleted; amino acids	
				125-135 deleted	
bcd^12	EMS	bcd^GB	2, 5	strong allele; 2486 C Æ T;	
				158 gln Æ amber	
bcd^13			3	hypomorphic allele	
bcd^14			3	hypomorphic allele	
bcd^15			4	strong hypomorphic allele	
bcd^16			4	strong hypomorphic allele	

^a

1 = Berleth, Burri, Thoma, Bopp, Richstein, Frigerio, Noll, and N  usslein-Volhard, 1988, EMBO J. 7:  1749-56; 2 = Fronh  ofer and N  usslein-Volhard, 1986, Nature 324:  120-25; 3 = Lambert, 1985, PhD Thesis, Indiana University; 4 = Seeger, 1989, PhD Thesis, Indiana University; 5 = Struhl, Struhl, and MacDonald, 1989, Cell 12:  59-73.

cytology:  Placed in region 84A1 on the basis of failure to be complemented by Df(3R)9A99 = Df(3R)83F2-84A1;84B1-2; Df(3R)LIN, and Df(3R)Scr = Df(3R)84A1-2;84B1-2, and complementation by Df(3R)4SCB = Df(3R)84A6-B1;84B2-3, and Df(3R)Antp17 = Df(3R)84A6;84D13-14.
molecular biology:  Gene identified in an 8.7-kb genomic fragment from coordinates -42 to -33 kb of the chromosome walk of Scott, Weiner, Hazelrigg, Polisky, Pirrotta, Scalenghe, and Kaufman (1983, Cell 35:  763-76) by germ-line transformants that completely rescue the mutant phenotype (Berleth, Burri, Thoma, Bopp, Richstein, Frigerio, Noll, and N  usslein-Volhard, 1988, EMBO J. 7:  1749-56; see also Frigerio, Burri, Bopp, Baumgardner, and Noll, 1986, Cell 47:  735-46; Kilchherr, Baumgardner, Bopp, Frei, and Noll, 1986, Nature 321:  493-97). The transcription unit comprises four exons and produces a major mRNA of 2.6 kb, which contains all four exons, and a minor 1.6-kb mRNA from which exons 2 and 3 are spliced. Splice-acceptor-site variation in the third exon leads to translation products of 489 and 494 amino acids (53.9 kd). The first exon contains a PRD repeat, consisting essentially of alternating histidines and prolines, found within a number of genes, including prd, expressed early in development; the 5   end of exon 3 encodes a novel homeodomain with no more than 40% amino-acid homology with other homeobox sequences; the 3   end contains a series of repeated glutamines, opa repeats. Also contains a RNA-recognition motif, mostly in exon 4 (Rebagliatti, 1989, Cell 58:  231-32). A highly acidic C-terminal domain is thought to provide transcriptional activation; the latter can be replaced with heterologous activating sequences and still display bcd^+ activity (Driever, Ma, N  usslein-Volhard, and Ptashne, 1989, Nature 342:  149-54). The sequence responsible for the anterior localization of bcd RNA at the anterior embryonic pole localized to 625 nucleotides in the 3   untranslated region, which include regions capable of forming extensive secondary structure (Macdonald and Struhl, 1988, Nature 336:  595-600). The ten residues from 138 to 147 comprise the DNA recognition helix of the bcd homeodomain; replacing the lysine in the ninth position of this ten-amino-acid sequence with either alanine or glutamine is sufficient to destroy recognition of hb sequences; in addition, the latter substitution confers a new specificity for Antp and Ubx upstream target sequences (Hanes and Brent, 1989, Cell 57:  1275-83). Bicoid protein binds to five high-affinity binding sites (consensus sequence TCTAATCCC) upstream from the hb transcription start site (Driever and N  usslein-Volhard, 1989, Nature 337:  138-43). The posterior boundary of the anterior hb domain responds to changes in the number or affinity of these sites as well as to the dose of bcd^+ such that increases cause a more posterior and decreases a more anterior boundary (Driever, Thoma, and N  usslein-Volhard, 1989, Nature 340:  363-67; Struhl, Struhl, and Macdonald, 1989, Cell 57:  1259-73).

Dfd:  Deformed
From Bridges and Morgan, 1923, Carnegie Inst. Washington Publ. No. 327:  94.

 Dfd:  Deformed 
location:  3-47.5.
references:  Chadwick and McGinnis, 1987, EMBO J. 3:  779-89.
Hazelrigg and Kaufman, 1983, Genetics 105:  581-600.
Jack, Regulski, and McGinnis, 1988, Genes Dev. 2:  635-51.
Kuziora and McGinnis, 1988, Cell 55:  477-85.
Martinez-Arias, Ingham, Scott, and Akam, 1987, Dev. 100:  673-83.
Merrill, Turner, and Kaufman, 1987, Dev. Biol. 122:  379-95.
Regulski, McGinnis, Chadwick, and McGinnis, 1987, EMBO J. 3:  767-77.
Chadwick, Jones, Jack, and McGinnis, 1990, Dev. Biol. 141:  130-40.
phenotype:  Null mutations act as recessive lethals. Homozygous or hemizygous animals die at the end of embryogenesis and show a spectrum of defects in the head. There are no discernible defects in the trunk. The head defects are associated with missing structures normally derived from the mandibular and maxillary segments, the dorsal lateral papillae of the maxillary sense organ, the mouth hooks, and the maxillary cirri. The remaining gnathal structures are present albeit disarranged likely due to abnormalities in the movements associated with head involution. A weak homeotic transformation (30-50% penetrance) has also been noted in animals hemizygous for a breakpoint-associated revertant of the single dominant gain-of-function allele (Dfd^rv1). The phenotype is an apparent transformation of the H piece and lateral-graten which appear to be replaced by cephalopharyngeal plates. This phenotype has not been observed in any other mutant genotype and the reason for its low-penetrance production by this particular allele is not known. X-ray-induced somatic clones of Dfd^- cells have shown that the locus is also required for adult head development. These cells develop normally in the thorax and abdomen but do not form structures in the ventral anterior aspect of the head; specifically the vibrissae and maxillary palps. Clones in the dorsal posterior part of the head form ectopic bristles which have been interpreted as a head to thoracic transformation. A temperature-conditional allele has been used to define two temperature-critical periods for Dfd^+ activity. The first is during embryogenesis during segmentation and head involution, while the second occurs in the late third instar larval through mid pupal stages. These times correlate nicely with the observed cuticular defects in mutant animals and the times of peak gene product accumulation. There is a single dominant gain-of-function allele which causes defects in the ventral aspects of the adult head similar to those seen in the Dfd^- head clones mentioned above. There are no defects seen in the posterior of the head nor does this allele cause any embryonic or larval defects as a heterozygote, homozygote, or hemizygote. This allele is associated with a group of B104 (roo) insertion elements (ca. 50 kb of inserted DNA) as well as a duplication of the 3   exons of the Dfd transcription unit (see below). The mutant causes an extended spatial domain of expression of the locus into the eye portion of the eye-antennal disc as compared to the pattern seen in normal animals. The precise cause-effect relationship between the observed molecular defect and the mutant phenotype is not known except that partial deletion of the B104 elements but not the 3   end duplication causes a reversion of the dominant phenotype and has no apparent effect on the wild type function of the resident Dfd gene. This dominant allele has been reverted and these revertants act as a simple recessive loss-of-function alleles with the one exception noted above. The Dfd transcript is initially detected at the blastoderm stage in a band of cells at the position of the future cephalic furrow. This RNA shows maximal accumulation from 6-12 hours of embryogenesis when it is found in the mandibular and maxillary lobes, as well as in the subesophageal reigon of the CNS. The amount of Dfd RNA diminishes through the first and second larval instars and peaks again during the third instar. At this point, it is found in the peripodial membrane cells of the eye-antennal discs. The cells which accumulate the RNA are those which have been fate mapped to give rise to the adult-head-capsule structures which are defective in Dfd^- clones. Antibodies raised to Dfd protein have shown a similar pattern of accumulation to that seen for the RNA. The protein is first detected in cellular blastoderm stage in a stripe of six cells which circumscribes the embryo. As germ-band elongation proceeds and segmentation becomes evident Dfd protein is detected in the mandibular and maxillary lobes and a portion of the dorsal ridge. During germ-band shortening protein is no longer detectable in the mandibular lobe or in the anterior lateral aspect of the maxillary lobe. The process of head involution carries the Dfd-expressing cells interiorly where they are found in portions of the pharynx at the end of embryogenesis. Dfd-positive cells are also found in the subesophageal region of the CNS in the maxillary ganglion. This expression pattern has been shown to be dependent on the prior expression of the gap and pair-rule segmentation genes for its inception and on an autogenous regulatory element upstream of the Dfd transcription initiation site for the maintenance of Dfd expression into the later stages of embryogenesis. Immunostaining of imaginal discs shows Dfd-positive cells in the peripodial membrane of the eye-antennal discs with no detectable accumulation in the disc proper. There are also a few cells in the stalk of the labial discs which appear to accumulate Dfd protein. The Dfd cDNA driven by a heat shock promotor has been returned to flies and used to ectopically express Dfd protein. Animals carrying this construct subjected to heat shock produce ectopic mouth hooks and maxillary cirri in the ventral aspect of their thoracic segments, two structures missing in Dfd^- animals. There is no phenotypic affect on abdominal pattern; however, head development is severely disrupted in heat-pulsed animals.
alleles:  

allele	origin	discoverer	synonym	type	cytology	
						
Dfd^1	spont	Cattell, 13g		dominant allele	normal	
Dfd^2	EMS	Cain	Dfd^rC9	hypomorphic allele	normal 	
Dfd^3	EMS	Cain	Dfd^rC11	temperature sensitive	normal	
Dfd^4	EMS	Fornili	Dfd^rf1	hypomorphic allele	normal 	
Dfd^5	EMS	Fornili	Dfd^rf78	hypomorphic allele	normal   	
Dfd^6	X ray	Kaufman	Dfd^rK2	null allele	? 	
Dfd^7	X ray	Kaufman	Dfd^rK26	hypomorphic allele 	? 	
Dfd^8	EMS	Matthews	Dfd^rKM2	hypomorphic allele	normal    	
Dfd^9	EMS	Matthews	Dfd^rKM24	hypomorphic allele	normal      	
Dfd^10	EMS	R. Lewis	Dfd^rR1	hypomorphic allele	normal       	
Dfd^11	EMS	R. Lewis	Dfd^rR3	null allele	normal 	
Dfd^12	EMS	R. Lewis	Dfd^rR11	hypomorphic allele	normal       	
Dfd^13	EMS	Merrill	Dfd^rV8	hypomorphic allele	normal        	
Dfd^14	EMS	Merrill	Dfd^rV13	hypomorphic allele	normal         	
Dfd^15	EMS	Wakimoto	Dfd^rW6	hypomorphic allele	normal          	
Dfd^16	EMS	Wakimoto	Dfd^rW21	null allele	normal           	
Dfd^rv1	X ray	Hazelrigg	Dfd^+RX1	Dfd^1 revertant	Tp(3;3)83D4-5;	
					84A4-5;98F1-2	
Dfd^rv2	X ray	Hazelrigg	Dfd^+RX13	Dfd^1  revertant	Df(3R)83E3;	
					84A4-5	
Dfd^rv3	X ray	Hazelrigg	Dfd^+RX16	Dfd^1  revertant	Tp(3;3)86F11;	
					87D14;84A4-5	
Dfd^rv4	X ray	Hazelrigg	Dfd^+RX17	Dfd^1 revertant	normal 	

cytology:  Placed in 84A4-5 by its inclusion in Df(3R)Scr, Df(3R)Antp17, and Df(3R)Dfd13 and the location of two revertant-associated breakpoints Dfd^rv1 and Dfd^rv2.
molecular biology:  The Dfd transcription unit has been identified in the ANTC by its association with two Dfd revertant breakpoints which interrupt it and result in the recessive lethal mutant phenotype. The identified transcription unit covers 11 kb of genomic DNA and is made up of five exons. The 5  -most three exons are separated by two relatively small introns and these are separated from the 3   -most two exons by a large 7-kb intron. Transcription proceeds from proximal to distal (with respect to the chromosome centromere to telomere). This orientation is opposite to that of all the other homeotic loci in the ANTC. The next most proximal gene in the complex is Ama, the 3   end of which is just over 20 kb from the 5   end of Dfd. Distally the 3   end of Dfd is 20 kb from the 3   end of Scr. The five exons sum to 2.75 kb, a figure in good agreement with the 2.8 kb transcript size seen in Northern blots. Sequence analysis of a full length cDNA shows a long open reading frame of 1758 nucleotides encoding a protein of 586 amino acids, yielding a molecular weight of 63.5 kd. The homeobox is encoded by exon four and the opa repeats are downstream in exon five.

 ftz:  fushi tarazu 
location:  3-47.5.
references:  Hafen, Kuroiwa, and Gehring, 1984, Cell 37:  833-41.
J  urgens, Wieschaus, N  usslein-Volhard, and Kluding, 1984, Wilheim Roux’s Arch. Dev. Biol. 193:  283-95.
Kuroiwa, Hafen, and Gehring, 1984, Cell 37:  825-31.
Laughon and Scott, 1984, Nature 310:  23-31.
Wakimoto, Turner, and Kaufman, 1984, Dev. Biol. 102:  147-72.
Weiner, Scott, and Kaufman, 1984, Cell 37:  843-51.
Carroll and Scott, 1985, Cell 43:  47-57.
Hiromi, Kuroiwa, and Gehring, 1985, Cell 43:  603-13.
Duncan, 1986, Cell 47:  297-309.
Hiromi and Gehring, 1987, Cell 50:  963-74.
Doe, Hiromi, Gehring, and Goodman, 1988, Science 239:  170-75.
phenotype:  Null loss-of-function mutations result in embryonic lethality. Animals survive to the end of embryogenesis and exhibit a pair-rule mutant phenotype in the cuticle. This same phenotype is observable in animals at the beginning of segmentation of the germ band. Prior to deposition of cuticle, ftz^- animals have two rather than three mouth (gnathocephalic) segments and five as compared to ten trunk metameres. The material deleted is derived from the even-numbered parasegments, ps2 through ps12. Similar metameric deletions/fusions are seen in the neuromeres of the ventral nerve cord of the CNS. The name of the locus derives from the phenotype and is Japanese for "segment" (fushi) "deficient" (tarazu) (N.B. — there is only one letter t in tarazu; it is at the start of the word i.e., there is no second t preceding the z). Temperature-sensitive alleles of the gene have shown that the temperature-critical period for viability and phenotype falls between 1 and 4 hours of embryogenesis with the mid point of 2.5 hours at the blastoderm stage. The recovery of clones of ftz^- cells created by X-ray-induced somatic exchange after cellular blastoderm have demonstrated that ftz^+ activity is not necessary for normal cuticular morphogenesis subsequent to this point in development. In addition to these recessive null and hypomorphic alleles there are two classes of dominant gain-of-function lesions at the ftz locus. The first, ftz-Regulator of postbithorax-like, causes a variable transformation of the posterior haltere into posterior wing. The second, ftz-Ultra-abdominal-like, is associated with a patchy transformation of the adult first abdominal segment toward third abdominal identity. The former (ftz^Rpl) lesion also shows a recessive loss-of-function phenotype while the latter class (ftz^Ual) has no discernable embryonic phenotype and is homozygous viable. The fact that these dominant alleles produce mutant phenotypes that mimic lesions in the BXC has been interpreted as demonstrating a regulatory link between the segment enumeration genes and the homeotics.
alleles:  

allele	origin	discoverer	synonym	type	cytology	
						
ftz^1	DEB	M. Bender	ftz^b54ts	hypomorphic allele	normal	
ftz^2	DEB	M. Bender	ftz^b5ts	hypomorphic allele	normal	
ftz^3	EMS	Cain	ftz^c15	null allele	normal	
ftz^4	EMS	Cain	ftz^clts	hypomorphic allele	normal	
ftz^5	EMS	Fornili	ftz^f47ts	hypomorphic allele	normal	
ftz^6	EMS	Kaufman	ftz^k5	null allele	normal	
ftz^7	EMS	Matthews	ftz^km13	null allele	normal	
ftz^8	EMS	K. Matthews	ftz^kmQ	null allele	normal	
ftz^9	EMS	R. Lewis	ftz^R13	null allele	normal	
ftz^10	EMS	R. Lewis	ftz^R14	null allele	normal	
ftz^11	EMS	Wakimoto	ftz^w20	null allele	normal	
ftz^12 ^a	EMS	J  urgens	ftz^7B 			
ftz^13	EMS	J  urgens	ftz^9H34 			
ftz^14	EMS	J  urgens	ftz^9093 			
ftz^15	EMS	J  urgens	ftz^E66 			
ftz^16	EMS	J  urgens	ftz^E193 			
ftz^Rpl	X ray	Duncan	ftz^Rpl	dominant allele	T(2;3)84A6-B1;41	
ftz^Ual1	EMS	E.B. Lewis	ftz^Ual1	dominant allele	normal	
ftz^Ual2	ENU	Chiang	ftz^Ual2	dominant allele	normal	
ftz^Ual3	EMS	Duncan	ftz^Ual3	dominant allele	normal	
ftz^Ual2rv1	EMS	Duncan	ftz^-	revertant of ftz^Ual2	normal	
ftz^Ual2rv2	X ray	Duncan	ftz^-	revertant of ftz^Ual2	normal	
ftz^Ual2rv3 ^b	spont	Duncan	ftz^-	revertant of ftz^Ual2	?	

^a

Associated with a 5-kb insertion element in the transcribed region of ftz.
^b

Behaves genetically as a deletion of ftz, Scr, and Antp.

cytology:  Placed in 84B1-2 based on its inclusion in Df(3R)Scr and the 3R breakpoint of T(2;3)ftz^Rpl, which is known to interrupt the coding region of the ftz transcription unit.
molecular biology:  The localization and identification of the ftz transcription unit within the ANTC has been accomplished through the mapping of ftz-associated aberrations in the DNA [ftz^11 and T(2;3)ftz^Rpl] and the rescue of ftz^- genotypes using P-element mediated transformation. The transcription unit is just over 2 kb in length and is made up of two exons of 800 and 980 base pairs and a single 150-base-pair intron. The open reading frame is 1,239 nucleotides long and initiates in the (800 bp) 5   exon. Conceptual translation of the open reading frame predicts a protein of 398 amino acids with a molecular weight of 43 kd. The most prominent motifs in the protein are the homeodomain (encoded in the second exon) and a PEST domain which may be important in the dynamic pattern of ftz expression. Northern blots have shown that the ftz transcript is accumulated in early embryos starting at about 2 hours (syncytial blastoderm), peaking shortly afterwards and declining at about 4 hours. These times are coincident with the temperature-sensitive-period data noted above. The spatial pattern of RNA accumulation is first seen as a broad band at syncytial blastoderm extending from the position of the future cephalic furrow posteriorly to about 15% egg length. At cellular blastoderm this broad single band resolves into seven transverse stripes which circumscribe the embryo. These stripes disappear as gastrulation proceeds and are gone by mid gastrulation. Protein accumulation lags behind the RNA and is first detected at cellular blastoderm in the seven-stripe pattern. The position and width of the stripes indicates that ftz expression occurs within the even-numbered parasegmental anlagen, which are missing in ftz^- animals. Subsequent to the ectodermal expression in the germ band, the ftz protein product is again detected in the later stages of germ-band shortening, in a subset of cells in each of the segmental ganglia of the ventral nerve cord. This expression continues to the end of embryogenesis and has been shown to be important in the proper morphogenesis of a specific set of neurons repeated in each ganglion. Transformation studies have resulted in the identification of at least three cis-acting upstream regulatory elements necessary for normal ftz expression. An 1-kb fragment just upstream of the start of transcription is necessary for the establishment of the striped pattern at cellular blastoderm. Another fragment just distal to this element is needed for expression in the CNS, while about 6 kb upstream is an element necessary for the maintenance of stripes. It has also been shown that this cis-acting maintenance element requires the presence of ftz protein and therefore that ftz is apparently autogenously regulated in the later stages of its expression.

 lab:  labial 
location:  3-47.5.
references:  Diederich, Merrill, Pultz, and Kaufman, 1989, Genes Dev. 3:  399-414.
Merrill, Diederich, Turner, and Kaufman, 1989, Dev. Biol. 135:  376-91.
Mlodzik, Fjose, and Gehring, 1988, EMBO J. 7:  2569-78.
phenotype:  Null mutations act as recessive embryonic lethals. Animals survive to the end of embryogenesis and have normal thoracic, abdominal, and caudal segments. However, the head is abnormal, and shows defects in derivatives of all of the gnathocephalic segments. There is no obvious homeotic transformation in these animals. Analysis of earlier stages shows abnormalities in the process of head involution. X-ray-induced clones of lab^- cells demonstrate that lab function is unnecessary for the development of the adult thorax and abdomen. However, clones in the head fail to develop normally and show deletions in the maxilla and eye. Dorsally the posterior head capsule is transformed toward an apparent thoracic identity. A temperature conditional allele has been used to show a temperature critical period between 6 and 14 hours of embryogenesis. This period coincides with an interval in which head involution, a process disrupted by lab^-, takes place. Antisera raised to lab protein have shown it to initially accumulated just anterior to the gnathocephalic region of the germ band at the early stages of segmentation. This protein also is found in a row of cells extending above the gnathal region in the procephalic lobe and more dorsally into the dorsal ridge. As segmentation, germ-band shortening and head involution proceed, the cells expressing the protein are involved in the process complexities of head involution. Finally at the end of morphogenesis, lab positive cells are found in the lateral aspects of the pharynx, the tritocerebral ganglia of the CNS, and the frontal sac. In addition to this expression in the head, lab protein is also found in endodermal cells at the posterior of the anterior midgut and the anterior cells of the posterior midgut. The position and movements of the cephalic cells accumulating lab is consistent with the interpretation that this locus is expressed in the intercalary or most anterior of the gnathal segments.
alleles:  

allele	origin	discoverer	synonym	comments	
					
lab^1	EMS	R. Lewis	lab^r9	hypomorphic allele	
lab^2	X ray	Kaufman	lab^k3	temperature-sensitive	
				allele	
lab^3	EMS	Fornili	lab^f7	hypomorphic allele	
lab^4	EMS	Fornili	lab^f8	null allele	
lab^5	EMS	Fornili	lab^f10	hypomorphic allele	
lab^6	EMS	Fornili	lab^f33	hypomorphic allele	
lab^7	EMS	Fornili	lab^f40	null allele	
lab^8	EMS	Fornili	lab^f56	hypomorphic allele	
lab^9	X ray	Abbott	lab^a76	null allele;	
				In(3R)84A1-2;84E	
lab^10	EMS	Merrill	lab^v14	hypomorphic allele	
lab^11	DEB	Seeger	lab^l5	null allele	
lab^12	DEB	Seeger	lab^l10	hypomorphic allele	
lab^13	DEB	Seeger	lab^lB1	hypomorphic allele	
lab^14	X ray	Diederich	lab^vd1	null allele;	
				(insertion)	
lab^15	X ray	Diederich	lab^vd2	hypomorphic allele;	
				(deletion)	
lab^16	X ray	Merrill	lab^vd21	null allele;	
				T(3;4)84A1-2;101	
lab^17	X ray	Merrill	lab^vd22	hypomorphic allele	
lab^18	X ray	Merrill	lab^vd35	hypomorphic allele	

cytology:  Placed in 84A1-2 based on its inclusion in Df(3R)Scr and the location of the proximal 3R breakpoints of two rearranged alleles In(3R)lab^9 and T(3;4)lab^16. These latter two breakpoints have been located in the DNA and are known to interrupt the lab transcription unit.
molecular biology:  The lab transcription unit is the most proximal in the ANTC and has been localized and identified by mapping the position of four lab^- associated rearrangements in the DNA (lab^9, lab^14, lab^15, and lab^16) and the rescue of lab^- animals by a minigene constructed from the transcription unit implicated by the breakpoints. The lab transcription unit is 17 kb in length, is made up of three exons and is transcribed from distal to proximal on the chromosome. Exons two and three are separated by a 245-bp intron and these from the 5   exon by a 13.8-kb intron. The open reading frame begins at nucleotide +239 in the first exon and extends through the third. Conceptual translation of the open reading frame predicts a protein of 629 amino acids and a molecular weight of 67.5 kd. Northern blot analysis detects a single Poly(A)^+ RNA of 3.0 kb, a size in good agreement with the identified exons of 1455, 416, and 935 bp. This RNA is first detected at 2-4 hours of embryogenesis and remains present through the larval and pupal stages. There is no detectable accumulation in adults. The encoded protein contains opa sequences as well as a homeodomain. The latter is encoded by sequences in exons two and three, has its closest similarity to the pb homeodomain, and shares with that homeobox the position of its intronic interruption.

 pb:  proboscipedia 
location:  3-47.5.
references:  Bridges and Dobzhansky, 1933, Wilhelm Roux’s Arch. Dev. Biol. 127:  575-90.
Kaufman, 1978, Genetics 90:  579-96.
Lewis, Wakimoto, Denell, and Kaufman, 1980, Genetics 95:  383-97.
Pultz, Diederich, Cribbs, and Kaufman, 1988, Genes Dev. 2:  901-20.
phenotype:  Null alleles transform the labial palps of the adult into portions of the prothoracic leg. The distal tarsal segments are present, including claws and pulvilli. The distal portion of the first tarsal segment including the sex comb in males is fused directly to the proximal portion of the femur. Thus proximal first tarsus, tibia, and distal femur are absent. Leg segments proximal to femur are not present. Hypomorphic alleles produce a labial-palp-to-antenna transformation. Generally only more distal (arista) antennal structures are seen. Extremely weak hypomorphic alleles exist which produce no ostensible phenotype as homozygotes but do reveal a weak antennal transformation in combination with a deletion or null allele. Both null and hypomorphic alleles also show an alteration in maxillary palp morphology which has been interpreted as a transformation toward an antennal identity.
alleles:  

allele	origin	discoverer	synonym	phenotype	cytology	
						
 pb^1	spont	Bridges and		18° Æ antenna	+	
		Dobzhansky		29° Æ leg	+	
 pb^2	g ray	Duncan and		leg	+ 	
		Kaufman				
 pb^3	g ray	Duncan and		leg	+ 	
		Kaufman				
 pb^4	g ray	Duncan and		antenna	+ 	
		Kaufman				
 pb^5	g ray	Duncan and		leg	+ 	
		Kaufman				
 pb^6	spont	Baker, W.K.	pb^72j	weak antenna	+	
 pb^7	X ray	Abbott	pb^a19	leg	+	
 pb^8	X ray	Abbott	pb^a21	leg	+	
 pb^9	X ray	Abbott	pb^a70	leg	+	
 pb^10	X ray	Diederich	pb^bd4	leg	+	
 pb^11	EMS	Cain	pb^c13	antenna	+	
 pb^12	X ray	Kaufman	pb^draw1	leg	+	
 pb^13	EMS	Fornili	pb^f4	weak antenna	+	
 pb^14	EMS	Fornili	pb^f73	18° Æ antenna	+	
				29° Æ leg		
 pb^15	EMS	Hazelrigg	pb^h62	antenna	+	
 pb^16	X ray	Kaufman	pb^lose1	leg	In(3LR)66B;84A4-5	
 pb^17	EMS	Matthews	pb^m1	leg	+	
 pb^18	EMS	Matthews	pb^m2	leg	+	
 pb^19	EMS	Matthews	pb^m3	leg	+	
 pb^20	X ray	Pultz	pb^map2	leg	Df(3R)84A4-5	
 pb^21	X ray	Pultz	pb^map3	leg	T(2;3)84A4-5;26D-F	
 pb^22	X ray	Pultz	pb^map6	leg	+	
 pb^23	X ray	Pultz	pb^map8	leg	+ (deletion)	
 pb^24	X ray	Pultz	pb^map9	leg	In(3R)84A4-5;84D	
 pb^25	X ray	Pultz	pb^map10	leg	In(3R)84A4-5;het	
 pb^26	X ray	Pultz	pb^map12	leg	In(3R)84A4-5;85D	
 pb^27	X ray	Pultz	pb^map13	leg	+ (deletion)	
 pb^28	X ray	Pultz	pb^map17	variegating leg	In(3R)84A4-5;het	
 pb^29	EMS	Merrill	pb^v10	leg	+	
 pb^30	EMS	Merrill	pb^v12	leg	+	
 pb^31	EMS	Wakimoto	pb^w4	18° Æ leg	+	
				29° Æ antenna		
 pb^32	EMS	Wakimoto	pb^w19	antenna	+	
 pb^33	X ray	Kaufman	pb^win1	leg	Df(3R)84A4-5;84B1-2	
 pb^34	X ray	Kaufman	pb^win3	leg	Df(3R)84A4-5;84C1-2	
 pb^35	X ray	Kaufman	pb^win5	leg	+	
*pb^36	X ray	Kaufman	pb^win12	leg	In(3R)84A4-5;87A5	
 pb^37	X ray	Kaufman	pb^x1	leg	+	
 pb^38	X ray	Kaufman	pb^x2	leg	Df(3R)84A4-5;84B1-2	
 pb^39	X ray	Kaufman	pb^x3	leg	T(2;3)44F;84D	
 pb^40	X ray	Matthews	pb^x4	leg	+	

cytology:  Placed in 84A4-5 based on its inclusion in Df(3R)Scr and the location of eleven pb-associated breakpoints in this doublet (see table of alleles).
molecular biology:  The pb transcription unit extends over 35 kb of DNA in the proximal portion of the ANTC. It is bounded distally by the z2 transcription unit and proximally by a cluster of at least eight cuticle-like genes. Neither the proximal nor distal transcripts have any demonstrable function in the fly. The transcription unit produces a single 4.3-kb mRNA which is derived from nine exons distributed over the interval. The open reading frame begins in exon two and ends in exon nine. The homeobox motif is encoded in exons four and five and is split by intron four in the same position as the homeobox is split in the labial gene. The opa sequences are in exon eight and are therefore downstream of the homeobox. Exon three is roughly equidistant between its two flanking exons and the two largest introns of the gene. This exon is 15 nucleotides long and is alternately spliced. The RNA and protein products of the gene are accumulated in the maxillary and mandibular lobes of the embryo and the labial discs of the larvae.

 Scr:  Sex combs reduced 
location:  3-47.5.
references:  Kuroiwa, Kloter, Baumgartner, and Gehring, 1985, EMBO J. 4:  3757-64.
Sato, Hayes, and Denell, 1985, Dev. Biol. 111:  171-92.
Mahaffey and Kaufman, 1987, Genetics 117:  51-60.
Martinez-Arias, Ingham, Scott, and Akam, 1987, Development 100:  673-83.
Riley, Carroll, and Scott, 1987, Genes Dev. 1:  716-30.
Carroll, DiNardo, O’Farrell, White and Scott, 1988, Genes Dev 2:  350-60.
Glicksman and Brower, 1988, Dev. Biol. 127:  113-18.
LeMotte, Kuroiwa, Fessler, and Gehring, 1989, EMBO J. 8:  219-27.
Mahaffey, Diederich, and Kaufman, 1989, Development 105:  167-74.
phenotype:  Null mutations at the locus result in embryonic lethality. Animals die at the end of embryogenesis and show evidence of homeotic transformation in the cuticle derived from the labial and first thoracic segments. The first thorax is transformed to a second thoracic identity and the labial segment toward maxillary. This latter phenotype is seen as a duplication of the maxillary sense organs and the cirri. Deletions of the locus as well as null alleles also produce a dominant phenotype most clearly seen in males as a reduction in the number of sex-comb teeth. This reduction is indicative of a partial transformation of first leg to second, a conclusion borne out by the recovery of hypomorphic alleles of the locus which as hemizygotes allow survival to the adult stage and have no obvious effect in the embryo. These survivors show a complete transformation of ventral prothorax to mesothorax including the presence of stenopleural bristles on the propleurae; they also show an apparent transformation of the dorsal prothorax toward a mesothoracic identity. In addition to these thoracic transformations, the labial palps are transformed toward a maxillary palp morphology. All of these adult transformations can also been seen in X-ray-induced somatic clones of Scr^- cells. Thus Scr activity is needed for proper segmental identity in both the embryo and adult in the anterior-most segment of the thorax and the posterior-most metamere of the head. In the absence of Scr product these two segments are transformed divergently to the identity of the next most posterior and anterior metamere respectively. The only other homeotic mutation to produce such a divergent homeosis is pb, which appears to act similarly in the adjacent maxillary and labial segments of the adult head. In addition to these loss-of-function mutations there are several gain-of-function dominant alleles. All result in a similar phenotype in adults, most clearly seen in males as the production of sex combs on the second and third thoracic legs. Additionally, strong alleles of this type (Scr^ScxW, Scr^ScxP, and Scr^ScxS) show the loss of sternopleural bristles indicative of a more complete transformation of mesothorax to prothorax. All of these dominants are associated with genomic rearrangements and with the exception of Scr^ScxS act as recessive lethals (Scr^Msc, Scr^ScxT1, Scr^ScxT2, and Scr^ScxP) or semilethals (Scr^ScxW and Scr^ScxT3) at the locus. Examination of animals carrying these lesions at the end of embryogenesis as heterozygotes with a normal chromosome or hemizygotes reveals no evidence of the gain-of-function transformation of T2 and T3 Æ T1, only the loss-of-function phenotypes described above. These phenotypic observations have been extended by showing that Scr protein is accumulated ectopically in the second and third leg imaginal discs in dominant gain-of-function genotypes but not in the second and third thoracic segments at any point in embryogenesis. Thus it appears that the spatial pattern of Scr expression is differentially regulated at these two times. Genetic analyses have shown that at least one difference lies in Scr imaginal expression being subject to a transvection-like effect. The gain-of-function lesions cause or allow the ectopic expression of the structural gene on the trans- rather than the cis-coupled transcription unit. This is most clearly seen in the case of Scr^ScxT1, which is broken within the transcribed portion of Scr and is therefore incapable of making a functional gene product. Scr mRNA is first detected in embryos in early gastrulae in a band of cells just posterior to the cephalic furrow. Protein is not detected at this time but later during germ-band elongation; it is found in the region of the labial lobe. Subsequently, during germ-band retraction, RNA and protein are detected in the first thoracic segment with the highest concentration at the anterior border of this segment. RNA and protein are also detected in the subesophageal region of the CNS in the labial ganglion and in mesodermal cells associated with the anterior midgut. As head involution proceeds, the Scr-expressing cells of the labial segment are carried inside where they are found associated with the pharynx and the mouthparts at the end of embryogenesis. In the third larval instar, protein is found in the prothoracic leg discs, the dorsal prothoracic discs, the labial discs, and a small group of cells in the stalk of the antennal portion of the eye-antennal disc where it attaches to the mouthparts. In addition to this disc expression, Scr protein is accumulated in the subesophageal region of the CNS. This spatial pattern of expression in the epidermis is consistant with the spectrum of defects seen in Scr^- animals and clones.
alleles:  

allele	origin	discoverer	synonym	type	cytology	
						
Scr^1	EMS	Denell	Scr^d8	null allele	normal	
Scr^2	X ray	Kaufman	Scr^k6	null allele	normal	
Scr^3	EMS	R. Lewis	Scr^r18	hypomorphic allele	normal	
Scr^4	EMS	Wakimoto	Scr^w17	null allele	normal	
Scr^5	EMS	Wakimoto	Scr^w22	hypomorphic allele	normal	
Scr^6	EMS	Fornili	Scr^f2cs	cold-sensitive	normal	
				hypomorphic allele 		
Scr^7	EMS	Fornili	Scr^f71	hypomorphic allele	normal	
Scr^8	EMS	Fornili	Scr^f76cs	cold-sensitive	normal	
				hypomorphic allele 		
Scr^9	X ray	Abbott	Scr^a68	null allele	In(3LR)77D;	
					84B1-2	
Scr^10	X ray	Abbott	Scr^a72	null allele	In(3LR)75B;	
					84B1-2	
Scr^11	EMS	Lambert	Scr^c12	null allele	normal	
Scr^12	EMS	Stephenson	Scr^e40	null allele	normal	
Scr^13	EMS	Matthews	Scr^km0	null allele	normal	
Scr^14	EMS	Matthews	Scr^km7	hypomorphic allele	normal	
Scr^15	EMS	Matthews	Scr^km12	hypomorphic allele	normal	
Scr^16	EMS	Matthews	Scr^km15	null allele	normal	
Scr^17	X ray	Pultz	Scr^p18	null allele	normal	
Scr^18	X ray	Merrill	Scr^VD30	null allele	In(3R)84B1-2;	
					95F	
Scr^19	X ray	J  urgens	Scr^XF5	null allele	T(2;3)?	
Scr^20	X ray	J  urgens	Scr^XT145	null allele	T(2;3)?	
Scr^Msc	spont	Tokunaga	Msc	Dominant allele	In(3R)84B1-2;	
					84F1-2	
Scr^W	EMS	Wakimoto	Scr^w15	Dominant allele	50 kb inversion in 84B1-2	
Scr^Wrv1	X ray	Hazelrigg		Scr^w revertant	T(2;3)58F1-2;	
					84B1-2	
Scr^Wrv3	X ray	Hazelrigg		Scr^w revertant	normal 	
Scr^Wrv5	X ray	Hazelrigg		Scr^w revertant	In(3R)81;84B1-2	
Scr^Wrv6	X ray	Hazelrigg		Scr^w revertant	T(2;3)22D;	
					63A1-2+	
					T(2;3)54A1;	
					80-81	
Scr^T1	X ray	Tiong	Scr^T1	Dominant allele	Tp(3;3)80-81;	
					84B1-2;84D5-6	
Scr^T2	X ray	Tiong	Scr^T2	Dominant allele	T(2;3)40-41;	
					84B1-2	
Scr^T3	X ray	Tiong	Scr^T3	Dominant allele	T(2;3)25D;40;	
					84B1-2+	
					T(2:3)29B;	
					91E	
Scr^P	X ray	Pultz	Scr^P1	Dominant allele	T(3;4)80-81;	
					84B1-2;102F	
Scr^S	DEB	Seeger	Scr^msl	Dominant allele		

cytology:  Placed in 84B1-2 based on its inclusion in Df(3R)Scr, and the common 84B1-2 breakpoints of eleven Scr mutations.
molecular biology:  The Scr transcription unit has been identified by the localization of twelve Scr-associated breakpoints and the overlap junction of six deletions. Three of these approach Scr from its distal limit [Df(3R)Antp7, Df(3R)A41, and Df(3R)Hu]; the remainder delete the proximal end of the gene [Df(3R)Dfd13]. The identified transcription unit spans 25 kb of genomic DNA and is made up of three exons. Proceeding from 5   to 3   they are 0.5, 1.0, and 2.5 kb in length. The two introns are 6.0 and 15 kb respectively. The 3   end of Scr is 20 kb distal to the 3   end of Dfd, and the 5   end of Scr is 18 kb proximal to the 5   end of ftz and 50 kb proximal to the 3   end of Antp. Breakpoint associated mutations in this latter 50-kb interval all affect Scr function indicating that this region is important for the normal expression of the transcription unit. The sum of the three identified exons is in close agreement with the 3.9-kb mRNA detected on Northern blots. There is a single large open reading frame, which initiates in exon 2 just downstream of the splice acceptor, and terminates in exon 3 about 300 nucleotides downstream of the splice acceptor. Thus the 3   tail is just over 2 kb in length. The total open reading frame is 1,245 nucleotides in length and encodes a protein of 413 amino acids with a predicted molecular weight of 45 kd. The homeobox motif is encoded in exon 3 and opa-like repeats are found in exon 2.

 z2:  zen-2 
location:  3-47.5 (inferred from close proximity to zen).
synonym:  zpr: zen pattern related.
references:  Rushlow, Doyle, Hoey, and Levine, 1987, Genes Dev. 1:  1268-79.
Pultz, Diederich, Cribbs, and Kaufman, 1988, Genes Dev. 2:  901-20.
phenotype:  Simultaneous deletion of both z2 and pb produces only a pb mutant phenotype. Thus absence of z2 function has no discernible effect on development or morphology.
cytology:  Placed in 84A4-5 based on its inclusion in Df(3R)Scr and exclusion from Df(3R)LIN.
molecular biology:  The z2 transcription unit maps 10 kb proximal to zen and about 1 kb distal to the transcription initiation site of pb. An open reading frame starts 67 bp downstream of the transcription start site in exon 1 and extends to 114 bp upstream of a consensus poly(A) addition site. The transcript produced is 1.0 kb in length and shows the same spatio-temporal expression pattern as the neighboring zen gene. Like zen conceptual translation of the z2 open reading frame reveals the presence of a homeobox domain (encoded in exon 2). This sequence shows good similarity to the zen homeobox (75%), but there is little other sequence similarity found in the remainder of the proteins. The function of this locus is not known, but in light of the fact that its deletion causes no detectable effect, and zen mutants can be rescued by a genomic fragment which does not contain z2, it is likely the locus represents a pseudogene. Consistent with this conclusion is the finding that a z2 homologue is not found in the ANTC of D. pseudoobscura.

 zen:  zerkn  ullt 
Location:  3-47.5 (between pb and bcd in the ANTC).
references:  Wakimoto, Turner, and Kaufman, 1984, Dev. Biol. 102:  147-72.
Rushlow, Doyle, Hoey, and Levine, 1987, Genes and Dev. 1:  1268-79.
Rushlow, Frasch, Doyle, and Levine, 1987, Nature 330:  583-86.
Doyle, Harding, Hoey, and Levine, 1986, Nature 323:  76-9.
phenotype:  Null mutations result in embryonic lethality and the loss of several dorsally derived embryonic structures, including the amnioserosa, optic lobe, and dorsal ridge. These animals also fail to fully extend their germ bands and go through the process of head involution. The name for the locus derives from the characteristic "wrinkled" appearance of the germ band seen in the SEM at the time of normal germ-band retraction. Hypomorphic mutations result in the absence of dorsal structures but do undergo normal gastrulation movements. A temperature-sensitive allele has been used to define the time of zen^+ action between 2 and 4 hours of embryogenesis, just prior to and overlapping the earliest observable morphogenic defects. X-ray induced somatic clones have further shown that zen^+ function is unnecessary for postembryonic development. The RNA product of zen is first detected at about 2 hours of development during the eleventh to twelfth cell cycle of the syncytial blastoderm. At this early stage the RNA is found on the dorsal surface of the embryo extending around the anterior and posterior poles. As cellularization proceeds and the early events of gastrulation begin, the RNA becomes restricted to a mid-dorsal stripe of cells. These cells have been fate mapped and give rise to the amnioserosa and the lobes in the dorsal posterior of the embryonic head, i.e., the structures absent in zen^- animals. The time of appearance of zen RNA also correlates nicely with the temperature-sensitive-period data obtained using the conditional allele. Antisera to the zen protein product has been used to follow its accumulation pattern, and this analysis agrees with and expands the in situ results. The protein is located in the nuclei of cells expressing the gene and at cellular blastoderm is found in a mid-dorsal stripe seven cells wide and seventy cells in length. During gastrulation these cells eventually give rise to the amnioserosa, the optic lobe, and dorsal ridge; these structures continue to show zen protein accumulation until the end of germ-band extension at about 4 to 6 hours of development. This end point also correlates well with the end of the temperature-sensitive period of the conditional allele. The spatial pattern of zen expression has been shown to be dependent on the products of several of the maternally expressed genes which specify the anterior-posterior and dorsal-ventral polarity of the embryo, and zen would appear to lie near the end of the axis-determining pathway.
alleles:  Seven ethyl-methanesulfonate-induced alleles, all of which have normal cytology.

allele	discoverer	synonym	comments	
				
zen^1	Fornili	zen^f16	temperature-sensitive	
			hypomorphic allele	
zen^2	Fornili	zen^f27	null allele 	
zen^3	Fornili	zen^f55	null allele 	
zen^4	Fornili	zen^f62	null allele 	
zen^5	Fornili	zen^f75	hypomorphic allele	
zen^6	Merrill	zen^v1	null allele 	
zen^7	Wakimoto	zen^w36	null allele 	

cytology:  Placed in 84B1-2 based on its inclusion in Df(3R)Scr and Df(3R)SCB-XL2.
molecular biology:  One of a pair of regions between pb and bcd in the ANTC has been shown to be zen by P-element mediated transformation and rescue of a zen^- genotype. The rescuing fragment is 4.5 kb in length and carries a single 1.3 kb transcription unit. It is composed of two exons separated by a 64-base pair intron. The start of translation is 52 base pairs downstream of the transcription start site in the first exon. The open reading frame ends 169 base pairs upstream of a poly(A) addition site in exon 2. The predicted size of mature message from genomic and cDNA sequence analysis is 1.3 kb which is in agreement with the transcript size observed on Northern blots. Conceptual translation of the open reading frame shows the presence of a homeodomain and PEST sequences, which are enriched for the amino acids serine, threonine, proline, and glutamic acid. The presence of both of these motifs correlates well with the DNA binding activity of zen protein and the dynamic pattern of protein accumulation seen for zen protein in vivo.

 antenna:  see ems

 Antennapedex:  see Apx

 Antennapedia:  see Antp under ANTC

 anterior open:  see aop

 anterobithorax:  see abx under BXC

 Antp:  see ANTC