Gene Dmel\da

da+ performs multiple roles during development. Maternally supplied da+ is required in female embryos as a positive activator of the gene, Sex-lethal (Sxl), the key binary switch gene for the sex determination pathway. Also, da+ expression is required in the somatic gonad of adult females for proper egg membrane formation, and hence for the survival of all progeny regardless of their sex. Embryonic expression of da+ is required in both sexes for the formation of the peripheral nervous system (PNS) and parts of the central nervous system (CNS). And, during larval and/or pupal stages, da+ may be required for the growth and/or differentiation of cells that form the adult cuticle. Amorphic alleles (da2, da3, da5, etc.) are recessive lethals, with a lethal period which is predominantly embryonic (Cronmiller and Cline, 1987; Caudy et al., 1988a). In addition, the hypomorphic allele, da1 (originally called da), is hemizygous [da1/Df(2L)da-] lethal (Mange and Sandler, 1973), and da1 homozygotes die when they undergo the first half of embryonic development at 29 (Cline, 1976). Death appears to be a consequence of dosage compensation defects (Cline, 1983a; Gergen, 1987). Viability of da1 homozygotes is improved by the presence of extra X or Y heterochromatin in either the parental female or her progeny (Sandler, 1972; Mason, 1973). Temperature-sensitive lethality of the da1 zygotic lethal effect is not affected by the Sxl genotype (Cline, 1980). da+ is not required in the germline, since da-(da2/da3) pole cells produce fertile gametes; however, mitotic recombination failed to yield significant da-(da2 or da3) somatic clones, suggesting da+ may be essential during epidermal development (Cronmiller and Cline, 1987). Embryos, homozygous for lethal da alleles, have a reduced CNS, lack all peripheral neurons, and have no external sensory structures (Caudy et al., 1988a). Adult flies heterozygous for a deletion of the achaete-scute (ASC) genes and simultaneously heterozygous for Df(da) (also da2/+ or da5/+) exhibit characteristic bristle defects (Dambly-Chaudiere et al., 1988). Hemizygosity for da+ reduces the number of supernumerary bristles in Hw mutants (Dambly-Chaudiere et al., 1988). In addition to its zygotic phenotype, da1 exhibits two separable maternal effects. There is a female-specific maternal effect: At 22 and 25, homozygous da1 females produce no daughters, while at 18, they produce approximately 20% as many daughters as sons (Cline, 1976). At 29, da1 displays a sex-nonspecific maternal effect. Homozygous females are reversibly sterile; they lay eggs that show little or no development (Cline, 1976). Sterility of da1 females at high temperature results from a defect in the somatic gonad rather than in the germline, since da- germ cells in wild-type ovaries produce normal eggs which support full viability of sons (Cronmiller and Cline, 1987). The female-specific maternal effect has a temperature-sensitive period which includes the last 60 hr of oogenesis and the first 3 hr of development (Cline, 1976). This maternal effect is also observed in crosses of da1 females to D. simulans males (Watanabe and Yamada, 1977). The female-lethal maternal effect is autonomous to the germline, as demonstrated by transplantation of da1, or da2/da3 pole cells into + hosts (Cline, 1983b; Cronmiller and Cline, 1987). Female zygotes from da1 mothers at 25 die as embryos. Such lethal female embryos show consistent abnormalities in midgut formation, and in about 50% of the abnormal embryos, shortening of the germ band fails, while anus and posterior spiracles open on the dorsal surface behind the head segments (Counce). Female embryos from da1 mothers also show consistent defects in the CNS, which is either reduced in width or shows abrupt bends or twists; abnormally formed gut often extends into the CNS (Caudy et al., 1988a). The majority of daughters of da1 mothers surviving at 18 are morphologically abnormal, often missing structures from one or more imaginal discs or abdominal histoblasts, and frequently with duplication of structures (Cline, 1976). Though it was reported that daughters of homozygous da1 females could be rescued by cytoplasmic injection (Bownes et al., 1977), the apparent rescue was subsequently found to result from nonspecific effects that may have slowed the early development of females who are on the threshold of surviving (Cline, 1984; see also Muir and Bell, 1987). Gynandromorphs can survive the lethal maternal effects, but there is no localized lethal focus. Diplo-X tissue develops abnormally alongside normally developing haplo-X tissue. Survival of the mosaics and their average fraction of diplo-X tissue increases with decreasing temperature (Cline, 1976). The da1 maternal effect masculinizes escaper daughters that are homozygous for mle (Cline, 1984) and masculinizes triploid intersex (XXAAA) progeny (Cline, 1983a). Females heterozygous for Sxl alleles that lead to male development develop as sterile males, mosaic intersexes, or sterile females (depending on the Sxl allele), when produced by da1 mothers (Cline, 1984). The da1 female lethal maternal effect is unaffected by tra or dsx (Bell, 1954; Colainne and Bell, 1968). However, daughters of da1/da1 mothers are almost fully rescued by a single zygotic dose of SxlM1 and to a limited degree by a duplication for Sxl+ (Cline, 1978). Conversely, zygotic Sxl- enhances the da maternal effect. Females with reduced Sxl dose (Sxl-/+) fail to survive from da1/da1 mothers at the semipermissive 18 (Cline, 1978). A strong dominant da maternal effect [da1/+, Df(2L)da/+, or da2/+ mothers] is observed when female progeny are doubly heterozygous for Sxl- and sis-a- (Cline, 1986, Genetics 113: 641-63; Cronmiller and Cline, 1986, 1987). The maternal effect of da1 is made semidominant also by E(da) (cis or trans to da1) in the mother (Mange and Sandler, 1973; see also Cline, 1980). The zygotic da+ dose itself does not affect expression of Sxl+ sex determination function (Cronmiller and Cline, 1986).