Viability good at 29 but ovaries of homozygous
females severely atrophied, probably with tumorous follicles.
At 25 cysts contain 16 nurse cells and no oocyte; females fertile when raised at 23. Mosaic studies indicate germ-line
function of gene (Perrimon and Gans, 1983, Dev. Biol.
Sxl: Sex lethal (T.W. Cline)
Sxl+ is a switch gene that acts throughout development to control all aspects of sexual dimorphism. Its products are required for female and must be absent for male
development. Uniquely among sex-determination genes, after
responding early in development to the primary sex-determination signal (the X:A ratio), Sxl maintains its own
activity state as well as that of the downstream genes with
which it interacts. It is required in a cell-autonomous
fashion for both germ-line and somatic female development. It
controls dosage compensation in females by suppressing
hyperactivation of X-linked genes. Mutations of Sxl fall into
two general classes: (1) recessive loss-of-function alleles
that are deleterious to homozygous females, but viable and
without phenotypic consequences in males, and (2) dominant
gain-of-function alleles that behave as constitutive mutations, dominant and deleterious in males but without adverse
effect in females, either heterozygous or homozygous. The
variety of functions of the Sxl gene can be affected differentially by mutations, accounting in part for the complex complementation pattern observed for the large array of diverse
mutant alleles. It is important to be aware that phenotypic
parameters of mutant alleles and allele combinations can be
very sensitive to culture conditions and genetic background.
A number of positive regulators of Sxl are known, including
the genes da, fs(1)A1621, sis-a, and sis-b. The female-specific lethal or sterile effects of mutations in these genes
are suppressed by gain-of-function Sxl alleles. Throughout
all but the very earliest period of development, female-specific expression of Sxl is known to be achieved by female-specific splicing of mRNA. The translation products from
these female-spliced RNAs appear to help maintain the female-specific (productive) RNA processing mode which generates
them, thereby establishing a positive feedback loop that maintains the female state throughout development.
Homozygous females invariably die as embryos but
hemizygous males are fully viable and fertile. In most wildtype genetic backgrounds, heterozygous females exhibit normal
viability and fertility, although occasionally display morphological defects characteristic of early cell death; however,
can be dominant semilethal for females in some wild-type
genetic backgrounds and under suboptimal growth conditions.
In doubly heterozygous combination with otherwise recessive
mutations in positive regulators of Sxl, this allele can
behave as a dominant: heterozygote viability is reduced for
daughters of da/+ females, as well as for females that are
also heterozygotes for either sis-a, sis-b or fs(1)A1621. In
some such doubly heterozygous situations, escaper females may
be incompletely masculinized (mosaic intersex). Homozygosity
for mutations in the autosomal male-specific lethal loci does
not suppress recessive Sxlf1 lethality, but it does partially
masculinize Sxlf1/+ females (generating mosaic intersexes) and
suppresses cell-death-related morphological defects. Homozygous moribund embryos show sex-specific alterations in the
phenotypic expression of hypomorphic X-linked alleles such as
run25, a reflection of upsets in dosage compensation (female
hyperactivation). Depending on the time of induction,
Sxlf1/Sxlf1 clones induced in Sxlf1/+ females can be phenotypically male and reduced in size. 2X:3A animals homozygous or
heterozygous for Sxlf1 are viable but masculinized. In
genetic mosaics and chimeras, Sxlf1 homozygous germ cells
develop abnormally and fail to generate functional gametes.
In some situations, the mutant female tissue displays masculine traits. Sxlf1 rescues males from the otherwise lethal
effects of a simultaneous duplication of sis-a+ and sis-b+.
Homozygous females are either inviable or very
poorly viable, depending on genetic background. Escapers are
invariably sterile but otherwise display no obvious sexual
abnormalities. Complements Sxlf2593. Homozygotes defective
in dosage compensation as indicated by hyperincorporation of
uridine by their polytene chromosomes. Allele fails to support oogenesis in germ-line clones induced by mitotic recombination.
A hypomorphic allele selected as an intragenic
suppressor of SxlM1 male lethality; maps 0.0065 cM to the
right of SxlM1. Only characterized in cis combination with
SxlM1. The double mutant is fully viable in males and poorly
viable in homozygous females, with escapers being phenotypically male and sterile. Hemizygous females are lethal. Partially complements Sxlf2593, generating true intersexes. Partially complements Sxlf7,M1 with escapers phenotypically male
and sterile. Fully complements Sxlfhv1. By itself, double
mutant fails to bypass maternal da+ requirement for activation, but can complement Sxlf7,M1 in this regard. Double
heterozygote with fs(1)A1621 is fertile.
A hypomorphic allele selected as an intragenic
suppressor of SxlM1 male lethality; maps 0.0099 cM to the left
of SxlM1. Only characterized in cis combination with SxlM1.
The double mutant is male viable and semiviable in homozygous
females. Escaper females are phenotypically male and sterile.
Hemizygous females are inviable. Double heterozygote with
fs(1)A1621 is sterile, like Sxlf1 but unlike SxlM1,f3. The
double-mutant allele retains some ability to rescue daughters
from the otherwise lethal maternal effect of da; however,
lowering maternal da+ activity appears to decrease Sxlf7,M1
functioning, consistent with other evidence that the parental
allele, SxlM1, is not fully constitutive. In the absence of a
wild-type Sxl allele, Sxlf7,M1 daughters that survive the da
maternal effect are phenotypically male and sterile; in contrast, the addition to this genotype of a wild-type Sxl allele
in trans renders survivors phenotypically female, but still
sterile with masculinized gonads. The latter genotype of
female is fertile provided mothers carry at least one da+
allele. The ability of Sxlf7,M1 to rescue daughters is
greatly enhanced by mutations in the autosomal, male-specific-lethal loci, genes involved in hyperactivation of X-linked genes in males. The basis for this enhancement is
related to the ability of these same mutations to enhance the
survival of Sxlf7,M1 hemizygous females. Although Sxlf7,M1
was used to demonstrate the ability of Sxl gene products to
activate Sxl+ alleles in trans, it can be inferred that this
allele is far below wild type in this activity. Sxlf7,M1 is a
dominant suppressor of sis-a female-specific lethality, generating sterile females remarkably similar to those described
above rescued from the da maternal effect. Unlike SxlM1,f3,
fails to complement Sxlf2593; yet partially complements
SxlM1,f3 and SxlfPb, generating sterile phenotypic males.
Allele supports oogenesis in homozygous mutant germ-line
clones induced by mitotic recombination. In males, mutant
allele suppresses the otherwise lethal effect of a duplication
of region 3C2-5A2; addition of Sxl+ to this aneuploid genotype
generates mosaic intersexes indicating that the positive
autoregulatory activity of Sxl products can bypass the X/A
signal. Double heterozygote with fs(1)A1621 is sterile (like
Sxlf1 and unlike SxlM1,f3).
A lethal hypomorphic allele defective in some very
early steps in the sex-determination process, but which has no
adverse effect on the growth or sexual development of homozygous mutant diplo-X clones induced by mitotic recombination.
Rare escapers at 18 are phenotypically female; nevertheless,
it has a dominant masculinizing effect on the phenotype of
triploid intersexes (2X:3A) and interacts in a dominant-lethal
fashion with mutations in da or sis-a, both early acting positive regulators of Sxl. Fully complements SxlfPR class (partial deletions of Sxl information that impair later functions
of the gene more than earlier). Complements SxlM1,fPa-ra.
A hypomorphic allele that is temperature sensitive
for most Sxl functions. Perhaps most notable for the fact
that homozygote viability can be quite high, with the females
developing as true intersexes (their specific grade of inter-sexuality depends on temperature). Lethal over a deficiency,
a null allele, or Sxlf7,M1 at any temperature; at permissive
temperatures, weakly complements SxlM1,f3 and hypomorphic
alleles of the SxlfPR class, generating (true) intersexual
escapers; complementation better with SxlfPb, generating
sterile females; fully complements Sxlf2, Sxlf9, and Sxlfhv1.
A subliminal allele, viable and fertile as homozygous females, but with greatly reduced viability in trans to
nulls. Polytene chromosomes of Sxlfhv1/Sxlf1 larvae that survive to third instar hyperincorporate uridine, revealing
female dosage compensation upsets. Mutation of mle appears to
partially masculinize this heteroallelic combination and may
slightly increase viability under some conditions. Sxlfhv1
homozygotes and heterozygotes display an increased requirement
for maternal da+ activity, suggestive of defects in early Sxl
A lethal hypomorphic allele that is able to initiate
female development, but is defective in its ability to maintain the female developmental commitment and/or to elicit
female sexual differentiation. It is masculinizing in homozygous mutant somatic clones induced by mitotic recombination,
and it causes the tissue in such clones to grow poorly;
nevertheless, it has no dominant effect on the sexual phenotype of triploid intersexes, nor does it interact in a dominant fashion with mutations in da or sis-a, both early acting
positive regulators of Sxl. Fully complements Sxlf9, which
appears to have a very different set of defects.
Female-lethal null allele that appears to be deleted
for the entire Sxl transcription unit. Males are fully
viable, fertile, and display normal male sexual behavior.
A hybrid-dysgenesis-induced apparent null allele
selected as an intragenic suppressor of SxlM1 male lethality.
Only characterized in cis combination with SxlM1. A P-element
insertion 5' to the site of the DNA insertion in SxlM1 but
still within the region of Sxl transcribed at all stages.
A hybrid-dysgenesis-induced derivative of SxlM1,fPa
selected for having regained the ability to complement Sxlf9.
This complex allele disrupts both male and female development,
with the magnitude of the effects in either sex depending on
culture temperature in a reciprocal fashion: high temperature
is more permissive for females and less permissive (more feminizing) for males. Intersexual males show little male sexual
behavior and stimulate courtship from other males. Dominant
male-lethal effects are greatly enhanced by the presence of a
duplication of Sxl+ in trans; male escapers with both alleles
exhibit an unusual dorsalization of the abdomen, their sternites being variably transformed into tergites.
A P-insertion-induced lethal hypomorphic allele with
the unusual distinction of displaying a mosaic intersex phenotype in homozygous mutant diplo-X clones induced by mitotic
recombination; hence, appears to be defective in the cellular
maintenance of the female sexual commitment. Under dysgenic
conditions, can mutate further to less extreme or to more
extreme condition. Partially complements Sxlf7,M1, generating
masculinized individuals; partially complements Sxlf2593, generating sterile females; fully complements Sxlf9.
Unconditionally lethal to males, even in the presence of a Sxl+ duplication. Retains normal level of female
function as evidenced by full viability and fertility of
homozygous and hemizygous mutant females. Recovered by virtue
of ability to bypass the normal requirement by females for
maternally supplied da+ product, a positive regulator of Sxl+;
however, bypass is incomplete at higher temperatures. Phenotype in both sexes results from expression of Sxl+ female sex
determination and dosage compensation functions largely
(though not completely) independently of the normal controls.
This is shown by the observation that induction of mutations
in cis that suppress dominant, male-specific lethality is
invariably associated with a corresponding reduction in Sxl+
female-specific activities and the dominant da maternal-effect
bypass phenotype. SxlM1 is lethal to most gynandromorphs by
the pharate-adult stage, disrupting the development of their
haplo-X tissue in a cell-autonomous fashion; mutant haplo-X
tissue in gynandromorphs is often, but not always, feminized.
This variable penetrance of the sex transformation suggests a
residual level of control by the X/A balance. SxlM1 feminizes
triploid intersexes, killing them as pharate adults, while
suppressing B and Hw alleles in a fashion consistent with
expectations for constitutive expression of normal female
dosage-compensation functions. Analysis of effects on the
dosage compensation of the very early acting segmentation
gene, run, suggests that constitutive expression of female
functions is not observed prior to the time when the later Sxl
promoter is required and RNA processing control is known to be
operating. Since run dosage compensation during this period
does require functioning of maternal da+, zygotic Sxl+, and
the X/A balance, the ability of SxlM1 to bypass these controls
during later stages of development would seem to indicate that
the effect of the mutant lesion it carries is on Sxl-RNA
splicing, a process that these other Sxl+ regulators may only
affect indirectly. The position of the SxlM1 mutant lesion in
the vicinity of the male-specific exon is suggestive in this
connection. Variable expressivity of this mutant allele may
underlie two additional observations: (1) SxlM1 male lethality
can be suppressed by fs(1)A1621, yet fs(1)A1621 female sterility can be suppressed by SxlM1, and (2) transplants of SxlM1/Y
and SxlM1/+ germ cells show that although the allele does not
appear to interfere with spermatogenesis in testes, it blocks
the otherwise masculinizing effect of testicular somatic tissue on diplo-X (female) germ cells.