# N: Notch (W.J. Welshons) The Notch locus is involved in the differentiation of the ectoderm and is found in band 3C7. It includes phenotypically distinct regions Ax, Co, fa, l(1)N, N, nd, and spl. The wild-type allele of Notch is essential for the proper develop- ment of the neurogenic region, appearing to direct some ecto- dermal elements into the epidermal pathway of development. The expression of the Notch phenotype depends on the dosage of N+, two doses in females and one in males being essential to produce wild-type flies. The mutant expression of N, charac- terized by notched wings as well as vein and microchaetal abnormalities (Mohr, 1919, Genetics 4: 285-82), is found in N/N+ females. l(1)N mutants, on the other hand, do not show a Notch phenotype over N+ and are lethal with N (Poulson, 1968, Proc. Int. Congr. Genet., 12th, Vol. 1: 143). Ax mutants show dominant wing and bristle phenotypes distinct from N (Foster, 1975, Genetics 81: 99-120; Portin, 1975, Genetics 81: 121- 33). Co is a duplication that affects wing veins when expressed in homo- and hemizygotes. The recessive visible mutants fa and spl affect the surface of the eye; in heterozy- gotes with N, the eyes are rough. Another recessive visible mutant nd (which includes fano = nd3) shows notched-wings, thickened veins, and interaction with N (Bauer, 1943, Z. Indukt. Abstamm. Vererbungsl. 81: 374-90; Welshons and Von Halle, 1962, Genetics 47: 743-59; Welshons, 1965, Science 150: 112-29). The expression of N+ during neurogenesis has been examined by in situ hybridization (Hartley, Xu, and Artavanis-Tsakonas, 1987, EMBO J. 6: 3407-17) and by antibody staining (Kidd, Baylies, Gasic, and Young, 1989, Genes Dev. 3: 1113-29; Johansen, Fehon, and Artavanis-Tsakonas, 1989, J. Cell Biol. 109: 2428-40). The protein is expressed in cells destined for neural and epidermal lineages and also in mesodermal cells. Later Notch expression is restricted to the neurob- lasts and their derivatives, the neurons and nerve processes. The use of temperature-sensitive mutants, especially l(1)Nts, has identified the TSP's for numerous defects at Notch (Shellenbarger and Mohler, 1975, Genetics 81: 143-62; 1978, Dev. Biol. 62: 432-46). Complementation between alleles can be understood as due to the spatial or temporal separation of defects in the course of development. The defects occur throughout developmental stages from embryo to late pupa. Notch mutants, recessive lethals, and visibles alter activi- ties of four enzymes of the mitochondrial respiratory chain (Thorig, Heinstra and Scharloo, 1981, Mol. Gen. Genet. 182: 31-38; 1981, Genetics 99: 65-74; Thorig and Scharloo, 1982, Genetics 57: 219-23). Construction of germ line mosaics homozygous for an N mutant reveal the existence of a maternal component of Notch expres- sion (Jimenez and Campos-Ortega, 1982, Wilhelm Roux's Arch. Dev. Biol. 191: 191-201), and Notch transcripts can be detected in unfertilized eggs (Artavanis-Tsakonis, Muskavitch, and Yedvobnick, 1983, Proc. Nat. Acad. Sci. USA 80: 1977- 81). Furthermore, N expression is generalized and not con- fined to tissues affected by mutant alleles; phenotypic effects, therefore, seem to be context-specific (Hartley et al., 1987). The Notch locus in D. hydei shares many similarities with the locus in D. melanogaster (Van Breugel, 1971, Genetica 42: 25-41; Van Breugel and Van Zyll Langhout, 1983, Genetics 103: 197-217). The components of Notch are described in separate entries on the following pages. cytology: Placed in 3C7 since heterozygotes for a mutation or a deficiency involving this band show the Notch phenotype (Slizynska, 1938, Genetics 23: 29-99; Demerec, 1939, Proc. Int. Congr. Genet., 7th, pp. 99-103; Demerec, Kaufman, Fano, Sutton, and Sansome, 1942, Year Book - Carnegie Inst. Washing- ton 41: 191). High resolution in situ hybridization and computer-aided optical microscope data collection and image analysis indicate that coding portions and introns of the Notch gene are contained in 3C7. DNA 5' to the transcription start site lies in the interband distal to 3C7 (Rykowski, Par- melee, Agard, and Sedat, 1988, Cell 54: 461-72). Relation to Co illustrated by three T(1;Y)'s with breakpoints in 3C: T(1;Y)D7, T(1;Y)R38, and T(1;Y)W17. The segmental dupli- cation formed from T(1;Y)D7 and T(1;Y)R38 is Confluens in phenotype; the corresponding deficiency is normal. The seg- mental deficiency formed from T(1;Y)R38 and T(1;Y)W17 is Notch in phenotype and the corresponding duplication is normal. In addition to T(1;Y)R38, two other translocations separate Co and N; T(1;Y)R30 and T(1;Y)J100 (Merriam and colleagues). Many N mutants have normal cytology. Translocations and inversions with a breakpoint at or near 3C7 also yield N mutants, some of which variegate for N and loci linked to it. Notch alleles identified as point mutations, inversions, translocations and transpositions are described in the mutant section as N and l(1)N, while N deficiencies are described in the deficiency section as Df(1)N. Deficiencies and inversions with a breakpoint in Notch can also recombine with mutant sites such that a systematic recom- binational analysis will identify the lesion at Notch on the genetic map (Welshons, 1974, Genetics 76: 775-94; Welshons and Keppy, 1981, Mol. Gen. Genet. 181: 319-24). molecular biology: Molecular cloning techniques have yielded a physical map of Notch in which a 37-40 kb transcription unit contains sequences homologous to a 10.5-11.7 kb poly(A)+ RNA; the DNA sequence of this transcription unit has been deter- mined (Kidd, Lockett, and Young, 1983, Cell 34: 421-33; Whar- ton, Johansen, Xu, and Artavanis-Tsakonas, 1985, Cell 40: 567-81; Yedvobnick, Muskavitch, Wharton, Halpern, Paul, Grimwade, and Artavanis-Tsakonas, 1985, Cold Spring Harbor Symp. Quant. Biol. 50: 841-54; Kidd, Kelley, and Young, 1986, Mol. Cell. Biol. 6: 3094-3108; Kidd and Young, 1986, Nature 323: 89-91; Kelley, Kidd, Berg, and Young, 1987, Mol. Cell Biol. 7: 1545-48; Kelley, Kidd, Deutsch, and Young, 1987, Cell 51: 539-48; Ramos, Grimwade, Wharton, Scottgale, and Artavanis-Tsakonas, 1989, Genetics 123: 337-48). Except for portions of the two largest intervening sequences, the 5' and 3' ends of the gene have been mapped, and the location of nine exons have been determined. The major Notch transcript encodes a stable 350 kd transmembrane glycoprotein (2,703 amino acids) which is expressed throughout development. The protein includes extracellular epidermal growth factor-like repeats with cysteines that probably form intramolecular disulfide bonds; different X chromosomes display frequent silent nucleotide substitutions in the EGF-like repeat region (Hartley et al., 1987; Kelley et al., 1987; Artavanis- Tsakonas, 1988, TIG 4: 97-100; Kidd et al., 1989; Johansen et al., 1989). P-element-mediated rescue of the homozygous lethal and heterozygous visible phenotypes of the mutants N5419 and N60g11 was accomplished with about 40 kb of genomic DNA car- ried in a Notch cosmid vector (Ramos et al., 1989). A 15-kb "minigene" of cDNA lacking most introns but carrying all the 10.2 kb exons was able to rescue nd and partially rescue faswb and spl, although it could not rescue fag and fano. The zero coordinate used in locating the molecular lesions in the various Notch alleles is the first EcoRI site in Canton-S DNA proximal to the 3C7 breakpoint of In(1)N76b8 (Kidd, Kelley, and Young, 1986, Mol. Cell Biol. 6: 3094-108; Kidd, Lockett, and Young, 1983, Cell 34: 421-33); it is 1.1 kb to the right of the zero coordinate used by Artavanis- Tsakonis et al., 1983. other information: Combined genetic and physical information is presented in the map of Notch . # Ax: Abruptex (W.J. Welshons) location: 1-3.0. phenotype: Homozygous females and males show shortened L5 vein, usually also L4, L2, and sometimes L3. Wings shortened, arched, and thin. Costal bristles clumped and frayed; costal veins thickened. Thorax shows midfurrow with rearranged hair directions; hairs on thorax and head fewer, with clear patches and streaks. Male genitalia often rotated. Ax/+ females show short L5 in half of the flies and sparse hair pattern on thorax. Lower temperature (19) markedly decreases expression, and higher temperature enhances it. Some Ax alleles enhance N expression in Ax/N heterozygotes, but others suppress the dom- inant N phenotype. For example, Ax/N8 approaches wild type in all characteristics. No wing-vein interruption in Ax/+ at 18 and 26, and enhancement by H occurs so that Ax/Y;H/+ and Ax/Ax;H/+ are nearly lethal at 26 (House, 1959, Anat. Record 134: 581-82). Ax/Ax;ciD/+ and Ax/Y;ciD/+ are lethal or nearly so at 26. At 22, males survive and show enhanced wing-vein interruption and more missing bristles. At 26, wing-vein interruption approaches 100% in Ax/+;ciD/+ (House and Lutes, 1975, Genetics 80: s42-43). Wing nicking is suppressed in Ax/N55e11 at 25, and Ax vena- tion is weakly expressed; Ax/Ax;Dp(1;2)51b/+ shows weak Ax venation (Portin, 1975, Genetics 81: 121-33). Nearly lethal when reared at 29; temperature-sensitive period early pupa (Portin and Sir'n, 1976, Hereditas 84: 109-16). In heterozy- gotes of Ax with the recessives at Notch at 18 and 25, there is neither expression of the recessive nor Ax-type venation. At 29, only Ax/fano shows some weak expression of the reces- sive, and all heterozygotes except Ax/nd2 show some Ax vena- tion (Portin, 1977, Hereditas 87: 77-84). Ax interacts with alleles Ax9, Ax59b, Ax71d, Ax16, and AxE2 (see appropriate entry). RK2 in males. alleles: Three classes of Ax mutations can be distinguished: Some alleles (Ax16, Ax71d and AxE2) in heterozygous combina- tion with N enhance the wing-incision phenotype; others (Ax1 and Ax9) suppress wing incision of N and in turn display suppression wing-vein gapping by N; yet another class (Ax59b and Ax59d) are homozygous lethal. Notch-enhancing and Notch- suppressing alleles are homozygous viable, but lethal in heterozygous : combination with each other. Phenotypic, cytological, and fine-structure mapping descriptions of these alleles appear below. allele origin discoverer synonym ref ( comments | _________________________________________________________________________ Ax1 / spont Nazarenko, Ax28 3, 6, 7, Asn986 -> Ile 28a 15 Ax9 / EMS Lefevre Ax9B2-2b 2, 3, 8, Asp948 -> Val 9, 10 Ax16 / EMS Lewis & Ax16172 1, 2, 3, Gly1174 -> Ala Bacher 8, 10 Ax59b /` X ray Green 3, 8, 10, Cys972 -> Gly 11, 12, 13 16 Ax59d /` X ray Green 3, 8, 11, Cys972 -> Tyr Ser 13, 16 GT replaced by ATATA Ax71d / X ray Portin & 3, 8, 10 Ser1088 -> Ile Ruohonen Ax75c EMS Welter Ax75c24 8, 13 Canton S AxE1 EMS 2 Oregon R AxE2 / EMS Foster 2, 3, 8, Oregon R 9, 10, 14 His1167 -> Tyr AxJ14 X ray 5 AxS spont Schalet l(1)16-55 4 Axtsl EMS Shellenbarger l(1)Axtsl 15 Oregon R ( 1 = Foster, 1973, Dev. Biol. 32: 282-96; 2 = Foster, 1975, Genetics 81: 99-120; 3 = Kelley, Kidd, Deutsch, and Young, 1987, Cell 51: 539-48; 4 = Kidd, Lockett, and Young, 1983, Cell 34: 421-33; 5 = Lefevre, 1974, DIS 51: 22; 6 = Mohr, 1932, Prox. Intern. Congr. Genet., 6th, Vol. 1: 190-212 (fig.); 7 = Nazarenko, 1930, Biol. Zentralbl. 50: 385-92 (fig.); 8 = Portin, 1975, Genetics 81: 121-33; 9 = Portin, 1977, Genetics 86: 309-19; 10 = Portin, 1977, Hereditas 87: 77-84; 11 = Portin, 1980, Hereditas 92: 303-07; 12 = Portin, 1981, Hereditas 94: 93-98; 13 = Portin, 1981, Hereditas 95: 247-51; 14 = Portin and Siren, 1976, Heredi- tas 84: 109-16; 15 = Shellenbarger and Mohler, 1975, Genet- ics 81: 143-62; 16 = Welshons, 1971, Genetics 68: 259-68; | Background on which mutation induced. / Mutants partially sequenced; each correlated with single amino acid substitutions within six adjacent EGF-homologous elements of the N protein; all have Gly at residue 2057 characteristic of Oregon R rather than Ser of Canton S (Kel- ley et al., 1987). ` Both alleles show changes in cysteine (cysteine to glycine in Ax59b, cysteine to tyrosine-serine in Ax59d). Develop- mental studies of Young have shown that Ax59d is a larval lethal and Ax59b is a pupal lethal (Kelley et al., 1987). # Ax1 phenotype: Temperature-sensitive lethal; male viable at 25 but nearly lethal at 29. Ax1/AxE2 semilethal at 25 and lethal at 29. Temperature-sensitive period for lethality of Ax1 at beginning of pupal stage; of Ax1/AxE2 at end of third instar and into early pupal stage. cytology: A single-band duplication, presumed to be for 3C7 by Schultz (Morgan, Schultz, and Curry, 1941, Year Book - Carne- gie Inst. Washington 40: 283). Lefevre, Ratty, and Hanks (1953, Genetics 38: 345-59), on the other hand, argue against a duplication for 3C7 on the basis of equal X-ray-induced mutability to N in Ax and +. Molecular information also incompatible with the presence of a duplication. molecular biology: Asparagine replaced by isoleucine at residue 986 in EGF repeat #25; AAT -> ATT (Kelley et al., 1987). Ax: Abruptex From Mohr, 1932, Proc. Intern. Congr. Genet., 6th, Vol. 1: 190- 212. # Ax9 phenotype: Viable in both sexes but poorly fertile or sterile. Bristle loss and vein interruptions are more extreme at 29. Heterozygotes of Ax9 with Ax1 and AxE1 are viable, but Ax9 is inviable with Ax71d, Ax16, and AxE2 (negative complementa- tion). The lethality associated with negative complementation is suppressed by 23 lethal Notch alleles as well as by alleles of Dl and mam (Xu, Rebay, Fleming, Scottgale, and Artavanis- Tsakonas). When heterozygous with N mutants, phenotypes of Ax and N tend toward normal, but there is temperature sensitivity for suppression of wing nicks (Foster, 1975; Portin, 1975). Ax9 complements every recessive visible on the Notch map at 18 to 29 (Portin, 1977, Hereditas, 87: 77-84); with Ax59b and Ax59d, it is semilethal. Negative complementation is elim- inated by Dp(1;2)51b and results in a strong Ax phenotype (Portin, 1975). The fate map for negatively complementing heteroallelic Ax9/AxE2 suggests a focus of lethality in tissue close to hypodermal sites of central thoracic structures; in surviving gynandromorphs, negative complementation for morpho- logical defects is autonomous (Portin, 1977, Genetics, 86: 309-19). molecular biology: Mutation results in an amino acid change from aspartic acid to valine at residue 948 in EGF repeat #24; GAC -> GTC (Kelley et al., 1987). # Ax16 phenotype: Homozygotes resemble Ax1. Ax16 is less fertile than alleles AxE2, Ax71d, and Ax9 (Portin, 1975), and temperature sensitive for the bristle and wing effects of Ax (Foster, 1975). In heterozygotes with Notch, Ax is expressed and the Notch wing effect is enhanced (Foster, 1975; Portin, 1975). At 29, heterozygotes with N are lethal. In Ax16/N264-40 heterozygotes, the TSP for lethality is in the second instar, and for Ax-morphological effects, it is in the third instar (Foster, 1973, 1975). In heterozygotes with recessive visi- bles at Notch, all are complementary at 18 and 25; at 29, there are mild indications of noncomplementarity with nd and nd2 (Portin, 1977). Heteroalleles Ax16/AxE2 and Ax16/Ax71d are viable (Foster, 1975; Portin, 1975); Ax16/AxE1 is inviable (negative heterosis) and heterozygotes with Ax9 and Ax1 are lethal (negative complementation) (Foster, 1975; Portin, 1975), but Dp(1;2)51b restores viability (Portin, 1977). Heterozygotes with the lethal alleles Ax59b and Ax59d are lethal and mostly inviable upon the addition of Dp(1;2)51b (Portin, 1975, 1977). cytology: Salivary chromosomes are normal (Foster, 1975). molecular biology: Mutation involves a change from glycine to alanine in residue 1174 in EGF-like repeat #29; GGA -> AGA (Kelley et al., 1987). other information: On the genetic map of Notch, probably between N264-40 and NCo based on the failure to obtain recom- binants between Ax16 and Ax9 (Foster, 1975). # Ax59b phenotype: Homozygotes and hemizygotes semilethal at 22; lethality approximates 100% at 25. Lethal in heterozygotes with N mutants but viable and fertile with recessive visibles at Notch. Ax59b/Ax59b; Dp(1;2)51b/+ are poorly viable and infertile, and mutant phenotype is enhanced. Ax59b/+; Dp(1;2)51b/+ females have diminished mutant expression com- pared to Ax59b/+ females which in turn are similar to males Ax/Y; Dp(1;2)51b/+. In heterozygotes with spl at 25, the eye is reduced in size but is larger than in spl/spl, and eye roughness varies from very mild to undetectable. The report by Welshons that Ax59b/spl did not express the split phenotype was an error caused by uncontrolled temperature variation. In cis heterozygotes, spl Ax59b/++, expression of split is enhanced compared to Ax59b/spl; the eyes are rough and reduced in size. No such enhancement is seen when fag is coupled to Ax59b, and in Ax59b/fag, the expression of the recessive is very mild and frequently nonpenetrant (Welshons, 1971). Ax59b is semilethal with Ax9 and lethal with alleles Ax16, AxE2, Ax71d, Ax1, and the addition of Dp(1;2)51b to heterozygotes of Ax59b with Ax9 and Ax1 restores viability (Portin, 1975). The temperature sensitivity of the Ax59b phenotype is strongest at 25; mutant expression decreases at both 18 and 29, with the least mutant expression at 29 (Portin, 1981, Hereditas 94: 93-98). At 18, there is complementarity with all reces- sive visibles at Notch and strong Ax expression in every case except when heterozygous with fag. At 29, all heterozygotes are noncomplementary with the exception of nd; Ax expression is diminished. At 29, homozygotes or hemizygotes with Dp(1;2)51b are more viable than at 18 or 25 (Portin, 1977). At 25, wing-vein interruption and bristle loss increases with an increased dose of the mutant gene (Portin, 1981, Hereditas 95: 247-51). Somatic crossing over yields twin spots on cuticular surface of flies, indicating that Ax59b is not a primary cell lethal (Portin, 1980). cytology: Salivary chromosomes normal (Welshons). molecular biology: Cysteine replaced by glycine at residue 972 in EGF repeat #24; TGC -> GGC (Kelley et al., 1987). Some Ax59b strains have acquired an eleven-base-pair deletion lead- ing to chain termination downstream of the substitution at residue 972, which is independent of the Ax59b lesion. Such double mutants show a typical N phenotype (Kelley et al., 1987). other information: Ax59b placed on the map of the Notch locus between spl and nd2; Ax59d placed between spl and NCo (Welshons). # Ax71d phenotype: Homozygous, viable, phenotype like Ax1. Viable with alleles AxE2 and Ax16, and lethal with Ax1 and Ax9 (negative complementation), but viability restored by Dp(1;2)51b. There is no obvious effect on the Notch phenotype in heterozygotes with N8 or N55e11, but Ax phenotype is expressed. In hetero- zygotes with AxE2, the mutant phenotype is weakly expressed; heterozygotes with lethal alleles Ax59b and Ax59d are lethal. Ax71d is complementary with recessive alleles at Notch at 18, 25, and 29. The mutant expression of Ax tends to increase with increasing temperature except that Ax71d/nd2 at 29 has no Ax expression. molecular biology: Mutation involves a change from serine to isoleucine at residue 1088 in EGF repeat #27; AGT -> ATT (Kel- ley et al., 1987). # Ax75c phenotype: Recessive lethal like alleles Ax59b and Ax59d. Ax75c/+ is temperature sensitive for pleiotropic effects; the variation in mutant expression with temperatures of 18, 25, and 29 resembles that of Ax59b and Ax59d with some variation in detail (Portin, 1981, Hereditas 94: 93-98). The Ax mutant phenotype increases with increasing dose of the allele (Por- tin, 1981, Hereditas 95: 247-51). # AxE1 phenotype: AxE1/+ females at 20.5 have gaps in wing veins and a reduction in number of ocellar and postvertical bristles. Semilethal as hemizygote or homozygote. Heterozygotes AxE1/Ax9 are viable and phenotypically intermediate: AxE1/AxE2 and AxE1/Ax16 are inviable (negative heterosis). AxE1 is inviable with most N mutants, but hetero- zygotes with N264-103 (a temperature-sensitive mutant) survive at 22 but not at 29. cytology: Salivary chromosomes are normal. other information: On the map of Notch to the right of fano and probably close to spl based on failure to obtain recombinants between AxE1 and spl. # AxE2 phenotype: Homozygous viable, phenotype like Ax1. Temperature sensitive for morphological phenotypes (Foster, 1975) but stable for viability (Portin and Siren, 1976). Viable in heterozygotes with N; Notch-wing phenotype is enhanced. At 18 and 25, complementary in heterozygotes with recessive alleles at Notch; at 29, spl and nd2 are weakly expressed (Portin, 1977, Hereditas 87: 77-94). Heterozygotes fano spl AxE2/+++ are like spl/spl with suppression of wing-vein gaps; fano++/+ spl AxE2 and +spl AxE2/+++ show mild expression of spl (Foster, 1975). AxE2 is viable with alleles Ax71d and Ax16; lethal with lethal alleles Ax59b and Ax59d and with AxE1, Ax9, and Ax1 (Foster, 1975; Portin, 1975), and the lethality with Ax1 is more pronounced at 29 (Portin and Sir'n). In AxE2/Ax1, the TSP for lethality is monophasic from the end of the third instar to early pupa (Portin and Sir'n, 1976). In AxE2/Ax9, the focus of lethality is close to hypodermal sites of ventral thoracic structures, and in surviving gynandromorphs, the negative interaction between alleles is autonomous (Portin, 1977, Genetics 86: 309-19). cytology: Salivary chromosomes are normal (Foster, 1975). molecular biology: Histidine replaced by tyrosine at residue 1167 in EGF-like repeat #29; CAT -> TAT (Hartley, Xu, and Artavanis-Tsakonas, 1987, EMBO J. 6: 3407-17; Kelley et al., 1987). other information: AxE2 is placed on the genetic map of Notch close to and to the right of spl (Foster). # AxJ14 phenotype: Male lethal, mutant phenotype similar to Ax1. Lethality is covered by Dp(1;2)51b and Dp(1;2)w64d, and males with the duplication show the Ax phenotype. When lethality is covered by w+Y, males have normal wing venation but lack ocel- lar bristles. In heterozygotes with fal2, females survive exhibiting a strong Ax phenotype and rough eyes. cytology: Salivary chromosomes normal. # AxS (A. Schalet) phenotype: Male and female homozygotes lethal. AxS/+ males and females show sparse thoracic hairs. AxS/Ax similar to Ax/Ax, viability strongly reduced. AxS/NS is lethal. Not suppressed by su(Hw)2. molecular biology: No detectable change in restriction map (Kidd et. al., 1983). # Axtsl phenotype: Ax phenotype 100% penetrant in heterozygotes at 18 and 29; homozygous lethal at 29 and semilethal at 18. Surviv- ing homozygotes have a stronger Ax expression than in hetero- zygotes. Lethal with N mutants at 29 and semilethal with Ax59d. Ax in phenotype and complementary with recessive visi- bles at Notch at 18 and noncomplementary at 29. other information: On the genetic map of the Notch locus to the right of spl. Co: Confluens Edith M. Wallace, unpublished. # Co: Confluens (W.J. Welshons) location: 1-3.0 [distal to N; not separated by recombination, but separated by T(X;Y) breakpoints (Merriam and colleagues)]. origin: Recovered among progeny of cold-treated fly. discoverer: Gottschewski 34c. references: 1935, DIS 4: 7, 14, 16. 1937, Z. Indukt. Abstamm. Vererbungsl. 73: 131-42. 1937, DIS 8: 12. phenotype: Veins irregularly thickened, especially toward tips, which are usually deltas and fused broadly to marginal vein. Stronger expression in males than in females. Co/N8 wild type except for slightly thicker L3 vein. Co/Ax like Ax/+. RK1A. cytology: Associated with a tandem duplication, Dp(1;1)Co = Dp(1;1)3C4-5;3D6-E1 (Schultz, 1941, DIS 14: 54-55). Result of duplication of 3C7, deficiency for which gives Notch (Mor- gan, Schultz, and Curry, 1941, Year Book - Carnegie Inst. Washington 40: 283). Relation to N illustrated by three T(1;Y)'s with breakpoints in 3C: T(1;Y)D7, T(1;Y)R38, and T(1;Y)W17. The segmental duplication formed from T(1;Y)D7 and T(1;Y)R38 is Confluens in phenotype; the corresponding defi- ciency is normal. The segmental deficiency formed from T(1;Y)R38 and T(1;Y)W17 is Notch in phenotype and the corresponding duplication is normal. In addition to T(1;Y)R38, two other translocations appear to separate Co and N: T(1;Y)R30 and T(1;Y)J100 (Merriam and colleagues). other information: Reversion to wild type occurs in Co/Co by unequal crossing over. # fa: facet (W.J. Welshons) location: 1-3.0. phenotype: Facet mutants affect the texture of the eye and in some cases cause slight to moderate wing nicks. Until now some recessive mutations with wing nicking but with normal eye texture have been designated as alleles of fa based upon their not being complemented by N mutants; in this treatment their designations have been changed to nd: notchoid, since they fail to complement nd mutants and like nd alleles, they com- plement fa alleles. All fa alleles complement spl, another eye-texture mutant in the N locus. alleles: Two general phenotypes: the facet phenotype has rough eyes owing to irregularities in size, shape and arrangement of ommatidia; eye color is uniform and wild type. The glossy phenotype also displays irregular facets, but the eye surface is smooth and pigment distribution may be uneven. Most of the alleles tabulated below are described in separate entries to follow. allele origin discoverer synonym ref ( comments | ________________________________________________________________________ fa1 spont Bridges, 7, 10, opus at 14b 13, 14 -11.9 to -11.2; weak allele; temperature sensitive; nicked wings; not dosage compensated fa3 spont / Welshons 7, 10, springer at 13 -11.9 to -11.2; intermediate allele; not temperature sensitive; dosage compen- sated *fado-vg spont 4, 6 wild type as hemi- and homozygote; fa with fa faDs ` spont Green 10 hopper at -15.0 to -14.2 fafx 3HTdR Kaplan, fx 2, 7, 8, flea at Hays 10, 13 -13.8 to -13.0; strong allele; not dosage compensated fag spont Pratt, 7, 10, 13, flea at 1962 17, 18 -10.3 to -9.4; strong allele; temperature sensitive; dosage compen- sated fag58 N-mustard Fahmy swb,fasw 3, 7, 10, "flea" at 12, 13 -11.9 to -11.2; strong allele; wings nicked; dosage compen- sated fag62 X ray Ives fag2, 7, 10, flea at swb62b 12, 13 -11.9 to -11.2; strong allele; wings nicked; dosage compen- sated fag88 - spont Kidd *fal Muller, 19h 15, 16 fal2 X ray Lefevre falN118 11 fan nd0 5 see nd fano nd3 1, 9 see nd fano69 nd4 see nd faswb X ray Lefevre swb71b 9, 12, 0.8 kb 19 deletion in -28.4 to -27.1 faswbBG 9, 10 flea at -11.9 to -11.2; wings nicked ( 1 = Bauer, 1943, Z. Indukt. Abstamm. Vererbungsl. 81: 374- 90; 2 = Craymer, 1980, DIS 55: 200; 3 = Fahmy, 1958, DIS 34: 49; 4 = Gardner, 1942, Univ. Calif. Publ. Zool. 49: 85-102; 5 = Glass, 1933, J. Genet. 27: 233-41; 6 = Goldschmidt, 1935, Biol. Zentralbl. 55: 535-54; 7 = Grimwade, Muskavitch, Welshons, Yedvobnick, and Artavanis-Tsakonas, 1985, Dev. Biol. 107: 503-19; 8 = Kaplan and Hayes, 1957, DIS 42: 38; 9 = Keppy and Welshons, 1977, Genetics 85: 497-506; 10 = Kidd and Young, 1986, Nature 323: 89-91; 11 = Lefevre, 1974, DIS 51: 22; 12 = Lefevre and Kelley, 1972, DIS 48: 146-47; 13 = Marko- poulou, Welshons, and Artavanis-Tsakonas, 1989, Genetics 122: 417-28; 14 = Morgan and Bridges, 1916, Carnegie Inst. Washington Publ. 237: 76; 15 = Muller, 1935, DIS 3: 30; 16 = Muller and Altenberg, 1921, Anat. Rec. 20: 213; 17 = Welshons, 1965, Science 150: 1122-29; 18 = Welshons, 1974, Genetics 76: 775-94; 19 = Welshons and Keppy, 1975, Genetics 80: 143-55. | Insertion of copia-like elements designated flea, hopper, springer, and opus into restriction fragments placed with respect to a zero point defined as the first EcoRI site proximal to the left breakpoint of In(1)N76b8. "flea" represents a derivative of flea in which 3 kb are replaced with 1.5 kb of foreign sequence (Kidd and Young, 1986). / Occurred in nd-bearing X. ` Ds = Drosophila simulans. - Phenotype like fag. Insertion in N intervening sequence. faswbBG is not faswb; it does not carry the faswb deletion; it is possibly a mislabled fag62, since it contains the same insert at exactly the same nucleotide. molecular biology: With the exception of faswb, the fa alleles that have been studied have copia-like inserts in a 0.1 kb region of the second intron of the Notch gene (in fa of Droso- phila simulans the insert is in the 3' end of the first intron). Five glossy-like alleles (fafx, fag, fag58, fag62, faswbBG) have the same element inserted, whereas each of three facet-like alleles (fa1, fa3, faDs) has a different inserted element (see allele table). In every case the orientation of the inserted element is such that they are transcribed in the opposite direction to that of Notch. # fa1 phenotype: Eyes of all males moderately rough owing to irregu- larity in size, shape, and arrangement of facets. Not dosage compensated; eyes of females less rough than those of males with about 10% overlap of wild type. Eye roughness of the females varies from nearly normal at 18 to marked at 29; pupal stage temperature sensitive (Shellenbarger and Mohler, 1975, Genetics 81: 143-62). Eye abnormality caused by overgrowth of secondary pigment cells, which compresses cones and causes overlying corneal facets to bulge (Waddington and Pilkington, 1942, DIS 16: 70). Wings have apical nicks in 0.25% of males and 0-5% of females. N/fa1 has rough eyes of fa1 as well as a Notch phenotype # fa3 phenotype: Eyes equally rough in both sexes; wings not notched. Eyes rougher than in fa males but not glossy as in fag; heterozygotes fa3/fag are rough, not glossy (Welshons). #*fado-vg: facet-dominigene for vestigial phenotype: By itself, it is wild type. fado-vg/fa1 shows rough eye character of fa1. fado-vg/fado-vg; vg/+ produces some wing notching. Presumed by Goldschmidt to enhance dominance of vg and thus termed a "dominigene". RK3. # fafx: facet-frostex phenotype: Strong echinus-like eyes, darkening with age with glistening frosted appearance. Homozygous females sterile, but sterility may be separable from fafx (Kaplan and Hayes, 1967, DIS 42: 38). # fag: facet-glossy phenotype: Eyes have facets more irregular than fa, but surface is smoothed, giving a glossy effect. Equal mutant expression in both sexes. Pigment distribution may be uneven, contribut- ing to an impression of altered eye color. No wing effect. Eyes of fag/fa1 intermediate between the two homozygotes. Complementary with spl, fano, nd, and nd2 (Welshons, 1965, Science 150: 1122-29). RK1. # fag58 phenotype: Large, rough eye with semiglazed surface and irregu- lar pigment distribution causing a patchy red color. About 2/3 flies have incisions of the inner wing margin. Viable and fertile as a male, reduced fertility in females (Fahmy, 1958, DIS 34: 49). # fag62 phenotype: Like fag and cannot be distinguished from it. In heterozygotes with N mutants and in fag62/fag, the fag pheno- type is exhibited; fag62/fa1 has a fa1 phenotype, and fag62/spl is wild type. #*fal: facet-lethal phenotype: fal/fa1 resembles fa1/fa1; not notched. Homozygous lethal. RK2. # fal2 phenotype: A male-lethal allele of Notch. Females nearly wild type but show occasional slight traces of Notch. Full comple- mentation with spl but interacts with fag showing rough irreg- ular eyes. # faswb: facet-strawberry phenotype: In males, eyes are rough with a variable tendency to be glossy; with fag and fag62, eyes are very rough, but mutant condition is not as extreme as that found in homozygous glossy-eyed mutants. In heterozygotes with fa1, eyes are slightly rough, overlapping wild type; with spl, the eyes are wild type. The faswb allele, like fa1, is not dosage compensated, and the mutant condition is poorly expressed in females. faswb/fano has slight deltas at junction of longitudinal veins with marginal veins; faswb complements nd and nd2; and in heterozygotes of faswb, N55e11 and N264-40, the eyes are glossy and the Notch phenotype is enhanced, resulting in reduced viability and fertility; with the temperature-sensitive N60g11, heterozygotes are less mutant, viable, and fertile. In double mutants, faswb fag, the males have fag-like eyes; and wing veins are thickened and delta like at tips; they resemble fano males except that wings are seldom notched. The wing-venation effect is less extreme in homozygous females (Welshons and Keppy, 1975, Genetics 80: 143-55; Keppy and Welshons, 1977, Genetics 85: 497-506). cytology: Deficiency for interband between 3C6 and 7, causing these bands to fuse (Keppy and Welshons, 1977). molecular biology: Caused by a deficiency of 800 base pairs in the restriction fragment -26.2 to -25.0 (Grimwade, Muskavitch, Welshons, Yedvobnick, and Artavanis-Tsakonas, 1985, Dev. Biol. 107: 503-19; this is 67 base pairs upstream from the start of transcription of Notch. Deletes the 3' end of the locus immediately to the left of N (Kidd, Kelley, and Young, 1986, Mol. Cell. Biol. 6: 3094-3108). other information: Removal of the region of 3C2-5 from the vicinity of faswb, either by deletion or inversion results in suppression of fuswb; also affected by spontaneously arising, cis-acting enhancer [e(faswb)] and suppressor [su(faswb)] mutations, both of which map to the 3C2-5 region. (Welshons and Welshons, 1986). # l(1)N: lethal (1) Notch (W.J. Welshons) location: 1-3.0. phenotype: There are four phenotypic varieties of l(1)N alleles: (1) Those that are lethal with N and wild type with the recessive visibles [see l(1)N1]; (2) Those that are lethal with N but not wild type with the recessive visibles [see l(1)N2, l(1)N3]; (3) Alleles whose heterozygotes with N+ have a phenotype not recognized as Notch [see l(1)NB], or (4) Alleles that are temperature sensitive for lethality and do not express a Notch phenotype in heterozygotes with N+ [see l(1)Nts]. The embryological defects in l(1)N1 are related to those in N; the development in l(1)NB is sufficiently normal to escape embryonic lethality (Poulson, 1967, 1968). alleles: allele origin discoverer synonym ref ( ___________________________________________________________________ l(1)N1 spont Welshons lN 3, 5, 6, 8, 10 l(1)N2 / ray Abrahamson lN2 3, 5, 6, 8, 10 l(1)N3 / ray Abrahamson lN3 3, 5, 6, 8, 10 l(1)N27-3 HD Gergen 2 l(1)N27-3rv | HD Kelley 2 l(1)N32/25/B | HD Shalet, Eeken 2 l(1)N37-10 | HD Gergen 2 l(1)N42-2 | HD Gergen 2 l(1)N57-4 | HD Gergen 2 l(1)N69e EMS Shellenbarger 7, 8 l(1)NB X ray Abrahamson 1, 3, 5, 8, 10 l(1)Nts1 / EMS Shellenbarger 4, 7-9 l(1)Nts2 EMS Shellenbarger 4, 7, 8 ( 1 = Arnheim, 1967, Genetics 56: 253-63; 2 = Kelley, Kidd, Berg, and Young, 1987, Mol. Cell Biol. 7: 1545-48; 3 = Kidd, Lockett, and Young, 1983, Cell 34: 421-33; 4 = Leh- mann, Jimenez, Dietrich, and Campos-Ortega, 1983, Wilhelm Roux's Arch. Dev. Biol. 192: 62-74; 5 = Poulson, 1967, DIS 42: 81; 6 = Poulson, 1968, Proc. Int. Congr. Genet., 12th, 1: 143; 7 = Shellenbarger, 1972, DIS 48: 55; 8 = Shellen- barger and Mohler, 1975, Genetics 81: 143-62; 9 = Shellen- barger and Mohler, 1978, Dev. Biol. 62: 432-46; 10 = Welshons, 1965, Science 150: 1122-29. | P-element insertion at 5' end of Notch transcription unit within 0.1 kb of transcription start site. l(1)N/+ = wild type; l(1)N/N and l(1)N/Y = embryonic lethal. Most hetero- zygous combinations with recessive visibles not tested. / Temperature shifts of mature larvae result in most ommati- dial cells becoming photoreceptors (Cagan and Ready, 1989, Genes Dev. 3: 1099-1112). # l(1)N1 phenotype: l(1)N1/+ females are wild type; l(1)N1/N females and l(1)N1/Y males are lethal; l(1)N/Y;Dp(1;2)51b males are Co- like. Heterozygotes with recessive visibles at Notch are wild type. Developmental defects in l(1)N1/Y males are more lim- ited than in N/Y males and the defects are confined to the anterior ectoderm (Poulson, 1967; 1968). Like N mutants, l(1)N1 mutants are defective as embryos (Shellenbarger and Mohler, 1975, 1978). molecular biology: l(1)N1 is associated with a 8.5 kb insertion between coordinates -24.2 and -23.0 about 2.3 kb to the right of the insertion associated with N55e11 (Kidd et al., 1983). # l(1)N2 phenotype: l(1)N2/+ females are wild type; l(1)N2/N females and l(1)N2/Y males are lethal. Heterozygotes with fa and fag are fa-like; with nd, they have nd-like wings and small eyes; with nd3, they are viable, fertile and nd3-like. Developmental defects in l(1)N2/Y males and time of lethal effect same as in l(1)N1/Y. Some l(1)N2/l(1)Nts1 females survive to late pupal stage (Shellenbarger and Mohler, 1975). # l(1)N3 phenotype: Same as l(1)N2. # l(1)NB phenotype: l(1)NB females have small eyes, fewer mesonotal bristles, and, sometimes, bald areas on the thorax (Welshons, 1965). The dominant bristle effect is more extreme in l(1)NB/Y;Dp(1;2)51b males than in l(1)NB/+ females. Heterozy- gotes with fa have fa-like eyes and, frequently, nicked wings; with nd, they show notched wings and thickened veins; with nd3, they are viable, fertile, and fa-like. l(1)NB/Y males die during early larval life (Poulson, 1967). l(1)NB/l(1)Nts1 females die before pupation (Shellenbarger and Mohler, 1975). Bristle effect autonomous in l(1)NB cells; homozygous mutant cells survive in mosaics (Arnheim, 1967). # l(1)N69e phenotype: l(1)N69e/l(1)N69e and l(1)N69e/Df(1)N-8 females are lethal at 18 and 29; l(1)N69e/+ heterozygotes are almost always wild type. l(1)N69e homozygotes die before pupation, but l(1)N69e/l(1)Nts1 heterozygotes survive until the pupal stage. # l(1)Nts1 phenotype: l(1)Nts1/+ females are wild type at 18 and 29, while l(1)Nts1/Df(1)N-8 females are lethal at 29, but a few escapers are found at 18. l(1)Nts1 homozygotes are viable at 18, but lethal at 29. If homo- and hemizygotes kept at 18C until eclosion are transferred to 29C and kept at this temperature for six days, they gradually become flightless and show gross histological changes in the flight muscles (Vikki and Portin, 1987, William Roux's Arch. Dev. Biol. 196: 12-15). Heterozy- gotes show recessive visible defects at 18, but not at 29. l(1)Nts1/l(1)N2 and l(1)Nts1/l(1)N3 females survive until the late pupal stage at 29. When heat pulses are given to pupae prior to sensillum-precursor-cell-determination, extra sen- silla are produced; when given after sensillum-precursor-cell determination, the precursor cells form neurons only, not accessory cells (Hartenstein and Posakony, 1990, Dev. Biol. 142: 13-30). # l(1)Nts2 phenotype: Similar to l(1)Nts1 except for occasional survival of homozygotes to the pupal stage at 29 and weaker expression of recessive visible defects in heterozygotes at this tempera- ture. # N: Notch (W.J. Welshons) location: 1-3.0. phenotype: Mutant alleles are characterized by the following types of expression: Wings of heterozygotes incised at tips and often along edges; veins L3 and L5 thickened; thoracic microchaetae crowded and irregularly distributed (Mohr, 1919, Genetics 4: 275-82; 1923, Z. Indukt. Abstamm. Vererbungsl. 32: 108-232). Males and homozygous females are lethal. In some N mutants, the phenotype is mild and varies in one or more of its typical features, but such N's can usually be identified by phenotypes expressed when heterozygous with recessive visible eye and wing mutants that also occur at Notch. Females N/N+ are Notch; females N/N+;Dp(1;2)51b (represent- ing a duplication for the Notch locus) are wild type. In the hemizygous male, N/Y is lethal, whereas N/Y;Dp(1;2)51b is viable and phenotypically normal; the wild phenotype is depen- dent upon the presence of the normal dosage of 3C6-7 for each sex. An extra dose of 3C6-7 [as in Dp(1;2)51b or Dp(1;1)Co] causes the expression of the dominant phenotype Confluens (Co); thus N+/N+;Dp(1;2)51b females and N+/Y;Dp(1;2)51b males are Co-like (Welshons, 1965). Deficiency mapping places Co to the left of N (Merriam). Homozygotes and hemizygotes for all N mutants suffer the same embryological defects. In developing embryos, the pat- tern of differentiation of anterior and ventral embryonic ectoderm is aberrant; both presumptive hypoderm and presump- tive neuroblasts develop as neuroblasts, resulting in embryos with a hypertrophied central nervous system lacking ventral and ventral-lateral hypoderm [Poulson, 1939, DIS 12: 64-65; 1940, J. Exp. Zool. 83: 271-325; 1950, Biology of Drosophila (M. Demerec, ed.). Wiley, New York, pp.168-274; 1967, DIS 42: 81; Wright, 1970, Adv. Genet. 15: 305-15]. Sensillum differentiation in peripheral nervous system of embryos also abnormal (Hartenstein and Campos-Ortega, 1986, Roux's Arch. Dev. Biol. 195: 210-21). In mosaic embryos (N/N+ and N/0 cells), the N/0 cells never give rise to hypoderm within the neurogenic region (Hoppe and Greenspan, 1986, Cell 46: 773- 83). However, single N/0 cells transplanted to N+ recipient embryos can give rise to hypoderm (Technau and Campos-Ortega, 1987, Proc. Nat. Acad. Sci. USA 84: 4500-04). alleles: Notch mutants and rearrangements (other than defici- ences) are described in the following tables, the first list- ing the extant alleles and the second the lost alleles. (Alleles that are also given a separate description are super- scripted "#"). Notch deficiencies are listed only as chromo- some rearrangements. N8 Mohr, 1924, Z. Induktive Abstammungs-Verebungslehre 32: 118. # N55e11 phenotype: A weak Notch. Deltas on wing veins are most reli- able character for classification. Lethal when heterozygous with nd3, N60g11, and NCo. In homozygotes and hemizygotes hyperplasia of central nervous system extreme; embryonic peri- pheral nervous system abnormal with sensilla undifferentiated (Hartenstein and Campos-Ortega, 1986, Wilhelm Roux's Arch. Dev. Biol. 195: 210-21). molecular biology: Lesion in Notch caused by a 3.5 kb insertion in the vicinity of coordinate -26, "+" values to the right, "-" values to the left (Kidd et al., 1983). # N60g11 phenotype: Wings seldom notched; veins thickened; deltas at tips. N60g11/+ heterozygotes have normal eyes at 29 and a disrupted facet arrangement at 21. With increasing tempera- ture, rough eye phenotype diminishes and Notch mutant charac- teristics are expressed. TSP for disrupted facets is in the third instar. N60g11/N60g11 Dp(1;2)51b7 females are viable at 29; survival sharply decreased at 20-23; TSP for lethality in middle of embryonic stage. N60g11/fa flies have eyes like fa. Semilethal with nd3. Viability poor with nd. # N64d6 phenotype: Typical Notch. N64d6 spl flies cannot be dis- tinguished from N64d6 spl+ flies. When spl is coupled to N64d6, spl is not enhanced by E(spl). Table I allele origin discoverer ref ( comments ______________________________________________________________________________________________________________________ N2 18, 20 N3b22 EMS Wieschaus 29 N22 like Nj24 N24/46A/1 | HD Schalet, Ecken 23 N30-4 | HD Gergen N30-4rv | HD Kelley wild type revertant N50k11 X ray Lefevre, 50k 26, 27 T(1;3)1E3-4;3C6-7;3C8-9;89A 3C7,3C8 missing N55e11 # spont Mohler, 55e 2, 3, 18, 20, 25, 29, 34, 37, 44, 48, 50 N60f10 / ray Ives 52 N60g11 # / ray Ives 13, 14, 44, 53 N60h21 / / ray Ives 52 N60j14 / / ray Ives 52 N61f19 / / ray Ives 53 N61h10 / / ray Ives 53 N62b10 / / ray Ives 52 N62l radio waves Mickey, 62l 33 N64d6 # X ray Judd 49 N66h26 # spont Green 3, 16, 24, 50, 51 In(1)3C1-2;3C7-8 N67k28 X ray 28 N68j # EMS Maddern, 68j 19 N68j1 # EMS Shellenbarger 40, 41 N68j2 EMS Shellenbarger 40, 41 N68l EMS Shellenbarger 40, 41 N69 NTG Kaufman 22 N69c # EMS Shellenbarger 40, 41 N69dt EMS Shellenbarger 40, 41 N69d2 EMS Shellenbarger 40, 41 N69d3 EMS Shellenbarger 40, 41 N69d4 EMS Shellenbarger 40, 41 N69d5 EMS Shellenbarger 40, 41 N69e1 EMS Shellenbarger 40, 41 N69e2 EMS Shellenbarger 40, 41 N69e3 EMS Shellenbarger 40, 41 N69f1 EMS Shellenbarger 40, 41 N76b8 # / ray Keppy 2, 3, 24, 51 In(1)3C7-9;3C9-10 N77c17 # X ray Keppy 2, 3 In(1)1D2-E1;3C7-9 N80j9 # unstable 17 In(1)3C6-7;3C7-9 revertant N81k2 X ray Muskavitch 17 N81k3 # X ray Muskavitch 17 N81k4 X ray Muskavitch 17 N81k5 X ray Muskavitch 17 N81k6 # X ray Muskavitch 3, 17 In(1)3C6-9;13A12-B2 N81k8 # X ray Muskavitch 2, 17 N81k9 # X ray Muskavitch 17 T(1;3)3C6-9;3L N81k10 # X ray Muskavitch 17 In(1)3C5-9;20A3-F N81l1 # X ray Muskavitch 17 In(1)3C5-9;20A3-F N81l2 X ray Muskavitch 17 N81l3 # X ray Muskavitch 2, 17 N81l5 # X ray Muskavitch 2, 3, 17 In(1)3C5-9;20A3-F N81l7 X ray Muskavitch 17 complex N81l8 X ray Muskavitch 17 N81l9 # X ray Muskavitch 2, 17 In(1)3C3-D3;20A3-F N264-6 ` X ray Demerec, 33k 4 Tp(3;1)N264-6 N264-10 ` X ray Demerec, 33l 8 T(1;2) N264-12 X ray Demerec, 34a 10, 21 T(1;4)3C6-7;101F N264-40 # X ray Demerec, 37d 2, 25, 29, 36, 37, 44 N264-47 # X ray Demerec, 37f 29, 36, 47 N264-58 - X ray Demerec, 38d 9 Tp(1;3)3B2-3;3D6-7;80D-F N264-66 # X ray Demerec, 38e 8 T(1;2)3C6-7;41 + T(1;2)7C9-D1;53F N264-84 - X ray Demerec, 39c 10 In(1)3C6-7;20 A-B N264-103 # X ray Demerec, 40a 13, 52 N264-107 # X ray Demerec, 40a 47, 48 N264-109 # X ray Demerec, 40a 25, 53 Nag like N264-12 NBH9 | HD Gergen 23 NCo # spont Welshons 37, 38, 45, 46, 52 NCo69 NTG Kaufman 22 ND13 | HD Schalet, Eeken 23 ND16 | HD Schalet, Eeken 23 ND30 | HD Schalet, Eeken 23 NDTV | HD Gergen 23 NFE1 X ray Campos-Ortega 29 NFE2 X ray Campos-Ortega 29 NFX1 X ray Campos-Ortega 29 NFX2 X ray Campos-Ortega 29 NFX3 X ray Campos-Ortega 29 NFX4 X ray Campos-Ortega 29 NFX5 X ray Campos-Ortega 29 NFX6 X ray Campos-Ortega 29 NFX7 X ray Campos-Ortega 29 NFX8 X ray Campos-Ortega 29 NFX9 X ray Campos-Ortega 29 NhdA171 # HD Engels 12, 17 NhdC8 # HD Engels 12, 17 NJ NTG Kaufman 22 Nj24 # spont Welshons 46, 52 NM # spont Mischaikow, 56l 7 NNic # X ray Nicoletti 44, 52 Nntg NTG Kaufman 22 NP P32 Bateman, 1950 8 NPI | HD Gergen 23 NS # spont Schalet 25 inserted DNA element NT NTG Kaufman 22 NW spont Williams, 56j 7 NX114 EMS Wieschaus 29 NXL86 EMS Wieschaus 29 NYi66 EMS Wieschaus 29 tsN69c see N69c ( 1 = Aronson, 1958, DIS 32: 67; 2 = Artavanis-Tsakonas, Grimwade, Harrison, Markopoulou, Muskavitch, Schlesinger- Bryant, Wharton, and Yedvobnick, 1984, Dev. Genet. 4: 233- 54; 3 = Artavanis-Tsakonas, Muskavitch, and Yedvobnick, 1983, Proc. Nat. Acad. Sci. USA 80: 1977-81; 4 = Ash- burner, Angel, Detwiler, Faithfull, Gubb, Harrington, Lit- tlewood, Tsubota, Velissariou, and Walker, 1981, DIS 56: 186-91; 5 = Barigozzi, 1940, DIS 13: 69; 6 = Bari- gozzi, 1942, Rev. Biol. (Perugia) 34: 59-72; 7 = Cicak and Oster, 1957, DIS 31: 80; 8 = CP627; 9 = Demerec, 1940, Genetics 25: 618-27; 10 = Demerec, 1941, Proc. Int. Congr. Genet., 7th, pp. 99-103; 11 = Demerec and Sutton, 1940, Proc. Nat. Acad. Sci. USA 26: 532-36; 12 = Engels, 1979, Proc. Nat. Acad. Sci. USA 76: 4011-15; 13 = Foster, 1973, Dev. Biol. 32: 282-96; 14 = Foster and Suzuki, 1970, Proc. Nat. Acad. Sci. USA 67: 738-45; 15 = Gottschewski, 1935, DIS 4: 15, 16; 16 = Green, 1967, Genetics 56: 467-82; 17 = Grimwade, Muskavitch, Welshons, Yedvobnick, and Artavanis-Tsakonas, 1985, Dev. Biol. 107: 503-19; 18 = Har- tenstein and Campos-Ortega, 1986, Wilhelm Roux's Arch. Dev. Biol. 195: 210-21; 19 = Hayman and Maddern, 1969, DIS 44: 50; 20 = Jimenez and Campos-Ortega, 1982, Wilhelm Roux's Arch. Dev. Biol. 191: 191-201; 21 = Judd, 1955, DIS 29: 126-27; 22 = Kaufman, 1970, DIS 45: 34; 23 = Kelley, Kidd, Berg, and Young, 1987, Mol. Cell Biol. 7: 1545-48; 24 = Keppy and Welshons, 1980, Chromosoma 76: 191-200; 25 = Kidd, Lockett, and Young, 1983, Cell 34: 421-33; 26 = Lefevre, 1951, DIS 25: 71; 27 = Lefevre, 1952, DIS 26: 66; 28 = Lefevre and Green, 1972, Chromosoma 36: 391- 412; 29 = Lehmann, Jimenez, Dietrich, and Campos-Ortega, 1983, Wilhelm Roux's Arch. Dev. Biol. 192: 62-74; 30 = Mather, 1942, DIS 16: 49; 31 = Meyer, 1952, DIS 26: 67; 32 = Meyer and Edmondson, 1951, DIS 25: 73; 33 = Mickey, 1963, DIS 38: 29; 34 = Mohler, 1956, DIS 30: 78; 35 = Oliver, 1937, DIS 7: 19; 36 = Poulson, 1939, DIS 12: 64-65; 37 = Poulson, 1967, DIS 42: 81; 38 = Poulson, 1968, Proc. Int. Congr. Genet., 12th, 1: 143; 39 = Ratty, 1954, Genetics 39: 513-28; 40 = Shellenbarger, 1972, DIS 48: 55; 41 = Shellenbarger and Mohler, 1975, Genetics 81: 143-62; 42 = Slizynska, 1938, Genetics 23: 291-99; 43 = Sutton, 1940, Genetics 25: 534-40; 44 = Thorig, Heinstra, and Scharloo, 1981, Genetics 99: 65-74; 45 = Welshons, 1956, DIS 30: 79; 46 = Welshons, 1958, Cold Spring Harbor Symp. Quant. Biol. 23: 171-76; 47 = Welshons, 1958, Proc. Nat. Acad. Sci. USA 44: 254-58; 48 = Welshons, 1965, Sci- ence 150: 1122-29; 49 = Welshons, 1971, Genetics 68: 259- 68; 50 = Welshons, 1974, Genetics 76: 775-94; 51 = Welshons and Keppy, 1981, Mol. Gen. Genet. 181: 319-24; 52 = Welshons and Von Halle, 1962, Genetics 47: 743-59; 53 = Welshons, Von Halle, and Scandlyn, 1963, Proc. Int. Congr. Genet. 11th, 1: 1-2. | Shows standard N phenotype in homo- and heterozygotes; no complementation of fa and fag. All except ND30 carry P- element insertions within 0.1 kb of N transcription start site (ND30 maps 0.3 kb downstream of start site). / N/fa lethal. ` XYY males viable, sterile. - N/fa variegates for fa. Table II allele origin discoverer ref ( phen. | cytology _________________________________________________________________________________________________________________ *N27 spont Mohr,30l 8 *N30 spont Mohr,38b 8 *N34b X ray Oliver,34b 35 T(1;3)N34b (?) *N40j spont Sismanidis,40j 30 *N47i UV Meyer,47i 31 *N51d UV Beyer,51d 31, 32 1 *N218 X ray Barigozzi 5, 6 1, 2 *N264-7 X ray Demerec,33k 8 In(1)3C6-7;3C8-9;8C5-7 3C7-8 missing *N264-8 X ray Demerec,33k 36, 42 3 *N264-9 X ray Demerec,33l 8 4 T(1;2)3C;41 *N264-20 X ray Demerec,34g 8 T(1;4)3C4-5;3C7-8;101F 3C5-7 missing *N264-23 X ray Demerec,35h 8 5 T(1;2)3C8-9;41A *N264-24 X ray Demerec,35h 10 T(1;2)3C8-9;40F *N264-29 X ray Demerec,36d 10 5 T(1;3)3D4-5;80 *N264-34 X ray Demerec,37a 10 3 T(1;3)3C3-5;70C2-3 *N264-48 X ray Demerec,37f 10 In(1)1B6-7;1B10-11;3C7-8 1B7-9 missing *N264-50 X ray Demerec,37k 10 1 Tp(1;2)3C7-9;20C1-F;22A2-3 *N264-52 X ray Demerec,38a 10 1 In(1)3C3-5;20B2-C1 *N264-53 X ray Demerec,38d 10 T(1;2)3C6-7;34C7-D1 *N264-55 X ray Demerec,38b 10 1 T(1;3)3D4-5;80F9-81F1 *N264-56 X ray Demerec,38c 8 T(1,3)3D4-5;80 *N264-57 X ray Demerec,38d 10 In(1)3C9-11;20D2-E1 *N264-59 X ray Demerec,38d 10 2 T(1;2)3C8-9;40F *N264-60 X ray Demerec,38d 8 *N264-62 X ray Demerec,38e 10 T(1;2)3C7-8;41A-B *N264-63 X ray Demerec,38e 10, 43 Tp(1;1)3C7-9;13C7-8;19F *N264-64 X ray Demerec,38e 10 T(1;3)3E5-6;80C-F *N264-65 X ray Demerec,38e 8 1 T(1;3)2B10-16;96C4-5 + T(1;3)3D4-5;81E *N264-69 X ray Demerec,38k 10 T(1;2)3C7-8;44C4-5 *N264-70 X ray Demerec,38k 43 1, 6 T(1;3)3C4-5;80D-F + T(1;3)6F2-7A1;100B2-3 *N264-71 X ray Demerec,38k 10 In(1)3C6-7;20D-F *N264-74 X ray Demerec,38k 43 1 T(1;2;3)3C10-11;20D-E;40C-D; 92E6-8 *N264-80 X ray Demerec,39d 10 Tp(2;1)3C6-7;36;40 + In(1)11;20 *N264-82 X ray Demerec,39d 8 1 T(1;2)3C3-4;41A + T(1;2)20A;57 *N264-83 X ray Demerec,39d 10 T(1;3)3C6-7;12F2-4;79E2-3 + In(3R)81;88 *N264-85 X ray Demerec,39d 9 1 T(1;2;4)3B4-C1;6A2-B1; 60A4-5;101F-102A *N264-86 X ray Demerec,39i 9, 11, 43 1 T(1;4)3C6-7;3C7-8;3E5-6; 101F *N264-87 X ray Demerec,39j 43 T(1;2;3)3C7-9;10A2-B1; 45F-46A;59F-60A;97C-D; 100E-F *N264-88 X ray Demerec,39j 8 *N264-91 X ray Demerec,39g 8 *N264-94 X ray Demerec,39k 8 *N264-95 X ray Demerec,39k *N264-97 X ray Demerec,39k 8 *N264-100 X ray Demerec,39l 9, 43 1 Tp(1;3)3B4-C1;4B4-5;80 *N264-102 X ray Demerec,39l 8 Tp(2;1)3C6-7;50E;56C *N264-104 X ray Demerec,39j 8 T(1;3)3C7-9;87D1-E1 + In(1)1B4-5;18-19 *N264-108 X ray Demerec,40a 8 In(1)3C3-5;3E7-8;20A4-5 3C5-3E7 missing *N264-112 X ray Demerec,40b 8 In(1)3C6-7;3F5-6 *N264-113 X ray Demerec,40c 43 T(1;4)3C10-D1;101 *N264-116 X ray Sutton,40e 8 In(1)2C8-10;3C7-9 *N264-119 X ray Demerec,40i 8 *N264-121 X ray Demerec,40j 8 T(1;3)3C7-9;81F;86B6-C1 *N264-122 X ray Demerec,40j 8 *N264-123 X ray Demerec,40k 8 *N264-124 X ray Demerec,41a 8 *N264-129 X ray Demerec,41c 8 *N264-131 X ray Demerec,41c 8 *NA spont Aronson 1 several bands to right of 3C4 deranged *NG heat Goldschmidt 15 ( See references following Table I. | 1 = Variegation for fa in N/fa; 2 = Variegation for spl in N/spl; 3 = Developmental abnormalities of male same as in Df(1)N-8; 4 = XYY male viable but sterile; XY male lethal; 5 = A few males, normal in phenotype, survive; 6 = Male viable and mottled for w and rst. # N66h26 phenotype: The Notch inversion N66h26 (synonym: In(1)w8xN66h26), with breakpoints in w and N, was derived from Df(1)N-8 and is unstable in crosses involving a wafagrb stock, giving rise to N+ revertants such as w8x1N+ and w8x2N+ (Welshons and Keppy, 1981; Grimwade et al., 1985). Recombina- tion hetween w and N, which does not occur in N66h26, does take place in these reversions, indicating that reversion to N+ is accompanied by reinversion of In(1)N66h26. The w8x1N+ derivative of N66h26 is also unstable in crosses involving the wafagrb stock, generating (stepwise) various mutant and wild- type Notch alleles (Grimwade et al., 1985). Df(1)w79, another derivative of N66h26, is deficient for both N and w (Welshons and Keppy, 1981). molecular biology: The lesion associated with the 3C7 break- point of N66h26 lies between -24.6 and -19.4 kb. # N68j phenotype: Typical Notch. N68j/+ females have wings excised at the tips; N68j/spl females are spl. N64j flies carrying Dp(1;1)Co are almost wild type. Mutant males with w+Y are viable (Hayman and Maddern, 1969). # N68j1 phenotype: Typical Notch. N68j1/Df(1)N-8 females are lethal at 29 and 18; Notch-wing phenotype shows little or no response to temperature (Shellenbarger and Mohler, 1975). # N69c phenotype: Shows variable Notch-wing expression depending on temperature. Lethal in homozygotes and in heterozygotes with Df(1)N-8 at 29 and 18. N69c/+ heterozygotes show greater expression of Notch-wing at 18 than at 29 (Shellenbarger and Mohler, 1975). # N76b8 phenotype: Typical Notch. molecular biology: The lesion associated with the 3C7-9 break- point lies between -2.2 and -1.3 kb on the physical map of Notch (Kidd et al., 1983). other information: Recombinational analysis indicates that the Notch locus distal to spl is in normal sequence. # N77c17 phenotype: Typical Notch. molecular biology: The lesion associated with the 3C7-9 break- point lies between -0.1 and 7.0 kb. other information: N77c17 does not recombine with N60g11 (Welshons). # N80j9 phenotype: Typical Notch. Genetically unstable, giving rise spontaneously to six independent N+ revertants. The N+10 revertant is rather unstable (Grimwade et al., 1985). molecular biology: The lesion associated with the 3C7-9 break- point of the inversion lies between -24.6 and -19.4 kb. # N81k3 phenotype: Typical Notch. molecular biology: This allele lies between -26.9 and -25.3 kb and seems to involve a deletion of 500 bp (Grimwade et al., 1985). # N81k6 phenotype: Typical Notch. molecular biology: The lesion associated with the 3C6-9 break- point of the inversion lies between +5.5 and +7.0 kb. # N81k8 phenotype: Typical Notch. molecular biology: This allele affects the restriction pattern of two regions at the same time (Grimwade et al., 1985), the first mapping between -10.6 and -9.5 kb and the second between -26.9 and -23.7 kb. Sequences between the fragments are unchanged as if N81k8 is an intralocus inversion. # N81k9 phenotype: Typical Notch. molecular biology: The lesion associated with the 3C6-9 break- point of the translocation lies between -25.3 and -23.7 kb. # N81k10 phenotype: Typical Notch. molecular biology: Mutant phenotype thought to be caused by position effect from the juxtaposition of the Notch DNA sequence and heterochromatin at 20A3-F (Grimwade et al., 1985). # N81l1 phenotype: Typical Notch. molecular biology: The lesion associated with the 3C5-9 break- point of the inversion lies between -19.4 and -9.5 kb. # N81l3 phenotype: Typical Notch. molecular biology: This allele lies between +0.9 and +3.7 kb and seems to involve a small deletion of 2200 bp (Grimwade et al., 1985). # N81l5 phenotype: Typical Notch. molecular biology: The lesion associated with the 3C5-9 break- point lies between 0 and +7.0 kb. # N81l9 phenotype: Typical Notch. molecular biology: The lesion associated with the 3C3-3D3 breakpoint lies between -16.7 and -9.5 kb. # N264-40 phenotype: Typical Notch. Male embryos show developmental abnormalities like those of Df(1)N-8 (Poulson, 1939). Lethal with nd3. molecular biology: Lesion associated with a 0.4 kb insertion between -6.2 and -5.6 kb on the physical map of Notch (Kidd et al., 1983). # N264-47 phenotype: Typical Notch. Male embryos show developmental abnormalities like those of Df(1)N-8 (Poulson, 1939). Lethal with nd3. other information: N264-47/spl heterozygotes produce nonrecom- binant N+ chromosomes with relatively high frequency (Welshons, 1958, Proc. Nat. Acad. Sci. USA 44: 254-58). # N264-66 phenotype: Wing-notching weak and rarely visible. N264-66/fa heterozygotes variegate for fa. Some N264-66/Y males are viable and have cream-colored eyes with spots of normal red pigment. # N264-103 phenotype: Temperature-sensitive Notch allele. N264-103/nd3 females are viable at 22o and lethal at 29o, with a long, possibly polyphasic, TSP beginning in the embryonic stage. N264-103/spl females show eye-facet disarray, notch- ing, bristle-number variation, and tarsal-segment fusion, the TSP being in the third instar (Foster, 1973). N264-103/spl variegates for spl; N264-103/fa is fa. # N264-107 phenotype: Typical Notch. other information: The N264-107 chromosome carries another Notch mutant site, l(1)N, at the distal end near N55e11 (Welshons, 1965). # N264-109 phenotype: Typical Notch except for semilethality with nd3. molecular biology: Lesion associated with a 14.8 kb insertion between +3.7 and +4.4 kb on the physical map of Notch (Kidd et al., 1983). # NCo phenotype: Wing tips seldom notched; veins thickened, with del- tas. Acrostichal rows irregular. NCo/nd3 heterozygotes lethal; rare survivors sterile and weak. NCo/+ females show thickened wing veins (a Confluens-like phenotype) more fre- quently than nicked or notched wings. Also, NCo heterozygous females with an extra dose of 3C6-7 [Dp(1;1)Co or Dp(1;2)51b] or hemizygous males with Dp(1;2)51b have an enhanced Confluens-like wing phenotype. # NhdA171 phenotype: Typical Notch. molecular biology: Lesion associated with a 6.3 kb insertion between -28.4 and -27.1 kb on the physical map of Notch. NhdA171 is the most distal of the dominant Notch alleles and is thought to be caused by a defective P-element (Grimwade et al., 1985). # NhdC8 phenotype: Typical Notch. molecular biology: Lesion associated with a 5.2 kb insertion between +2.7 and +3.7 kb, the insertion carrying moderately repetitive DNA sequences (Grimwade et al., 1985). # Nj24 phenotype: Typical Notch. Lethal with nd3. # NM: Notch Mischiakow phenotype: Wings notched at tips and occasionally at sides; veins thickened, with deltas. Eyes slightly smaller than nor- mal; occasionally one eye extremely small. molecular biology: The Notch locus in the reverted chromosome N+M contains an insertion homologous to the FB4 foldback ele- ment (Grimwade et al.). # NNic: Notch Nicoletti phenotype: Typical Notch. Lethal with nd3. Cell lethal in ter- gites and dorsal mesothorax (Ripoll and Garcia-Bellido, 1979, Genetics 91: 443-53). # NS: Notch Schalet synonym: l(1)16-178. phenotype: Weak Notch. NS/AxS is lethal. molecular biology: Lesion associated with a five kb insertion between +3.5 and +2.90 kb on the physical map of Notch (Kidd et al., 1983). # nd: notchoid (W.J. Welshons) location: 1-3.0. phenotype: Wings notched and veins thickened. The notching is found mostly on anterior and posterior margins and is the result of cell death (Thompson and Spivey, 1984, Genet. Res. 44: 201-69). Homozygotes are viable and fertile in both sexes. N/nd1 heterozygotes are partially viable and relatively infertile (Portin, 1977) and show notched and straplike wings and small eyes. About 10% of fa/nd1 flies have small notches in one or both wings. nd3/nd1 heterozygotes have slightly thickened wing veins with deltas; spl/nd1 heterozygotes lack a few bristles (like spl/+) and their eyes are sometimes smaller than normal and roughened. spl nd1 males have rough eyes, nd-like wings, and irregular, bushy sex combs. alleles: allele origin discoverer synonym ref ( _________________________________________________________________ nd0 X ray Glass, 1929 fan 4 nd1 TEM Fahmy, 1951 nfah 2, 3, 6-9, 11 nd2 R.M. Valencia, 6, 8, 10, 11 nd3 X ray Bauer fano 1, 8, 9, 11, 12 nd3.1072 spont R. Berg 5 nd3.1072rv R. Berg 5 nd4 EMS Shellenbarger fano69db 8 and Mohler ndts69d EMS Shellenbarger 8 ndts69f EMS Shellenbarger 8 ndts69j EMS Shellenbarger ndts69j3 8 ndts70j EMS Shellenbarger 8 ( 1 = Bauer, 1943, Z. Indukt. Abstamm. Vererbungsl. 81: 374-90. 2 = Fahmy, 1958, DIS 32: 72; 3 = Foster, 1973, Genetics 73: 435-38; 4 = Glass, 1933, J. Genet. 27: 233-41; 5 = Kelley, Kidd, Berg, and Young, 1987, Mol. Cell Biol. 7: 1545-48; 6 = Kidd, Lockett, and Young, 1983, Cell 34: 421-33; 7 = Portin, 1977, Hereditas 87: 77-84; 8 = Shellenbarger and Mohler, 1975, Genetics 81: 143-62; 9 = Welshons, 1965, Science 50: 1122-29; 10 = Welshons, 1971, Genetics 68: 259-68; 11 = Welshons, 1974, Genetics 76: 775-94; 12 = Welshons and Von Halle, 1962, Genetics 76: 775-94. cytology: Salivary chromosomes are normal (Fahmy). nd0 (= fan) From Glass, 1933, J. Genet. 27: 233-41. # nd0 synonym: fan: facet-notched. phenotype: Wings have apical nicks or notches in 90-100% of males, but only 8% of homozygous females. Eyes not rough. fa/nd0 is wild type. Viability and fertility excellent. RK2 in male. cytology: nd0 is on an In(1)dl-49 chromosome, and has not been separated from the inversion. # nd1 phenotype: nd1 is temperature-sensitive. In homozygotes at 29, the eyes are rough and reduced in size, there is extreme wing notching, and wing veins are thick; at 25, the abnormalities are less severe, and at 18, the eyes are normal and the wings are nicked. At 29, heterozygotes with fa, fag, and spl are complementary (Foster, 1973; Shellenbarger and Mohler, 1975). nd1/Y;E(spl)r19/+ males have severely reduced and crumpled wings (Xu, Rebay, Fleming, Scottgale, and Artavanis-Tsakonas). Wing development also affected in nd1/Y;mam10/+ males. nd1 and mam10 double heterozygotes are wild type. Wing notching is suppressed in nd1/Y males by Dl/+. molecular biology: nd1 maps at the 3' end of the Notch locus and carries a three bp insertion in the opa repeat producing an extra glutamine and a missense mutation resulting in a threonine to isoleucine change (Xu et al.). # nd2 phenotype: nd2/nd2 and nd2/nd1 flies resemble nd1 homozygotes; nd2/nd3 heterozygotes are noncomplementary (Welshons). The nd2 allele is temperature sensitive; in homozygotes at 29, the eyes are small and rough (spl-like), wings have extreme notches, wing veins are thickened, tarsi are shortened, and the mutants are semilethal as late pupae; at 25, the abnormal- ities are much less severe; at 18, the eyes are slightly spl- like, wings are nicked, wing veins are incomplete, some bris- tles are missing, and the mutants are semilethal as late pupae. At 29, fa/nd2 heterozygotes have nicked wings, spl/nd2 heterozygotes are spl-like, and nd4/nd2 heterozygotes resemble N/+ (Shellenbarger and Mohler, 1975). Similar wing abnormali- ties in nd1/Y;E(spl)r19/+ and nd2/Y;E(spl)r19/+ males. The temperature-sensitive rough-eye phenotype of nd2 is enhanced by E(spl)/+ (Xu et al.). molecular biology: nd2 maps proximal to nd1 at the 3' end of Notch and shows a deletion of one bp. # nd3 synonym: fano: facet-notchoid. phenotype: Wings of both sexes notched at ends of L3 and L4 veins; wing veins enlarged and delta-like at tips. Mild mutant expression often limited to wing-vein effect. Mutant expression diminished at high temperature (Shellenbarger and Mohler, 1975, Genetics 81: 143-62). Heterozygotes show extremely weak dominance. nd3/N almost completely lethal; survivors are sterile and have an exaggerated Notch phenotype. nd3/fa closely resembles wild type. Heterozygotes with fag and spl are complementary; with nd and nd2, heterozygotes are noncomplementary with a mild mutant expression of nd3-like wings. Up to 5% of nd3 males from aged cultures show hyper- and hypodeveloped external genitalia (Kroeger, 1960, J. Mor- phol. 107: 227-32). # nd3.1072 phenotype: Viable when homo- or hemizygous; shows adult wing nicking. Lethal when heterozygous with N deficiencies. Phenotype similar to nd. molecular biology: Associated with 1.2 kb P-element insertion within 0.1 kb of N transcription start site (Kelley et al., 1987). Unlike nd and nd2, occupies left end of genetic map. # nd3.1072rv phenotype: Wild-type revertant of nd3.1072. Viable in combina- tion with N deficiencies. molecular biology: Retains 200 bp of the original 1.2 kb P- element insertion (Kelley et al., 1987). # nd4 synonym: fano69. phenotype: Temperature sensitive and semilethal in homozygotes; wing phenotype more extreme and survival greater at 18 than at 29. nd4/+ lethal at both temperatures. # ndts69d phenotype: Like ndts69j (see below). # ndts69f phenotype: Like ndts69j (see below). # ndts69j phenotype: Temperature-sensitive semilethal. Homozygotes express weak notches, mild deltas, and extra bristles at both 18 and 29; both homozygotes and hemizygotes show significantly better survival at 18 than at 29. ndts69j/+ heterozygotes have normal wings at 18 and 29. Df(1)N-8/ndts69j heterozy- gotes have significantly better survival at 18 than at 29. # ndts70j phenotype: In general, ndts70j homozygotes and heterozygotes resemble the other Nts mutants. ndts70j homozygotes, however, are wild type at 18 and some ndts70j/+ heterozygotes have notched wings at 29. # spl (W.J. Welshons) location: 1-3.0. origin: X ray induced. discoverer: Dubinin. synonym: shd; fa3. references: Serebrovsky and Dubinin, 1930, J. Heredity 21: 259-65. Agol, 1931, Genetics 16: 262. Dubinin, 1934, DIS 1: 10. Welshons and Von Halle, 1962, Genetics 21: 743-69. Welshons, 1971, Genetics 68: 259-68. Foster, 1973, Dev. Biol. 32: 282-96. Shellenbarger and Mohler, 1975, Genetics 81: 143-62. Hartley, Xu, and Artavanis-Tsakonas, 1987, EMBO J. 6: 3407- 17. Kelley, Kidd, Deutsch, and Young, 1987, Cell 51: 539-48. Cagan and Ready, 1989, Genes Dev. 3: 1099-1112. Shephard, Broverman, and Muskavitch, 1989, Genetics 122: 429-38. phenotype: In homozygotes, eyes are rough and small, bristles are often doubled or split (sometimes missing). Hemizygotes show a more extreme reduction in eye size as well as an increase in facet and bristle abnormalities (Shephard et al., 1989). Both eye and bristle abnormalities occur at all tem- peratures from 18 to 29, an exception being a spl stock from Novosibirsk, Russia, that shows temperature sensitivity (Mglinetz, 1980, DIS 55: 107-08). The bristle phenotype is caused by an extra division of an initial bristle-forming cell (Lees and Waddington, 1943, Proc. R. Soc. London, B 131: 87- 110; Van Breugel and Van der Aart, 1979, Dev. Biol. 186: 267-71). A few bristles (sockets remaining) are usually removed from the posterior border of tergites in spl/+ hetero- zygotes (Welshons). The eye abnormalities are the result of abnormal differentiation of photoreceptors at the morpho- genetic furrow (Cagan and Ready, 1989). Heterozygotes with the other recessive visibles at Notch are almost normal except for spl/nd2 flies; the latter are spl-like at 29 (Shellen- barger and Mohler, l975). Another temperature-sensitive effect is shown by N264-103/spl flies, which have abnormal eye facets at 28-29 but are almost wild type at 20-22 (Foster, 1973, Dev. Biol. 32: 282-96). The spl phenotype can be enhanced by E(spl)/+ or E(spl)/E(spl). spl/+;E(spl)/+ flies resemble spl/spl flies; spl/spl; E(spl)/+ and spl/Y; E(spl)/+ flies show a very extreme mutant phenotype (Shephard et al., 1989). spl/Y;E(spl)R19/+ males and spl/+;E(spl)R19/+ females show spl and Ax-like phenotypes (Xu et al.). The spl pheno- type is reduced in mam heterozygotes. When, however, spl is coupled to a N point mutant, as in N64d6 spl/+ +;E(spl)/+, the phenotype is not spl (Welshons, 1971) split behaves auto- nomously in mosaics in regard to both eye and bristle pheno- types (Stern and Tokunaga, 1968, Proc. Nat. Acad. Sci. USA 60: 1252-59). The spl phenotype becomes dominant if spl is coupled, in cis, to lethal Ax alleles. Thus Ax spl/++ is spl, while +spl/++ is wild type (Welshons, 1971; Kelley et al., 1987). alleles: Three alleles have been reported: spl, *spl2, spl66c29. cytology: Salivary chromosomes normal. Placed in 3C7 on the basis of the interaction of split with Notch. molecular biology: spl cloned and sequenced. Located on the molecular map of N to the right of fag at about +2 kb. It is a missense mutation in the fourteenth EGF-like repeat in the extracellular domain of the putative N protein and involves a change from thymine to cytosine causing an isoleucine-to- threonine substitution at residue 578 (Hartley et al., 1987; Kelley et al., 1987). #*spl2 origin: Spontaneous. discoverer: Gottschewski, 1935. phenotype: Resembles spl except for smaller eyes. # N-2G: see mam #*N-b: Notch-b location: 2- (not located). origin: Spontaneous. discoverer: Mann, 1921. synonym: Notch 2. references: 1923, Genetics 8: 27-36. Morgan, Bridges, and Sturtevant, 1925, Bibliog. Genet. 2: 232. phenotype: Resembles Notch. Wing nicked in about 10% of heterozygous flies. Homozygote probably lethal. RK3. other information: Possibly a vg or mam allele.