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).
