sdc-2 is the likely zygotic activator of hermaphrodite-specific development in C. elegans, serving as a genetic switch in the sexual fate decision. Unlike the other genes that coordinately control sex determination and dosage compensation,
sdc-2 is the only gene whose product is made exclusively in developing XX embryos in response to the X:A ratio.
sdc-2 is essential for the activation of dosage compensation: its activity is required for the localization of the dosage compensation complex to the X chromosome. XX
sdc-2 mutant embryos die as a consequence of the overexpression of X-linked genes, while XO mutant animals are unaffected. In addition,
sdc-2 mutants fail to implement hermaphrodite sexual differentiation: the rare escapers of the XX-specific lethality are highly masculinized. We tested
sdc-2s ability to act as a switch gene by expressing
sdc-2 in developing XO embryos, where it is not normally active. If the expression of
sdc-2 is sufficient to activate hermaphrodite development in XO embryos, these animals should die as a result of reduced levels of X-linked transcripts. Indeed, the ectopic expression of
sdc-2 from the constitutive
dpy-30 promoter does cause extensive XO-specific lethality, suggesting that
sdc-2 activity is capable of activating the hermaphrodite mode of dosage compensation inappropriately in XO embryos. Two lines of evidence further support this interpretation. First, the XO-specific lethality associated with
dpy-30::
sdc-2 is rescued by a mutation in
sdc-3, another gene required for the coordinate control of hermaphrodite sex determination and dosage compensation in XX animals. Second, expression of
sdc-2 inappropriately directs the localization of a dosage compensation complex to the single X chromosome of
dpy-30::
sdc-2 XO embryos. Such X chromosome localization is required for the dosage compensation process and normally occurs only in XX embryos. If
sdc-2 does promote hermaphrodite development when expressed in XO embryos, it would be expected to implement not only the hermaphrodite mode of dosage compensation, but hermaphrodite sexual differentiation as well. Our hypothesis predicts that
dpy-30::
sdc-2 XO animals that are rescued by a dosage compensation-specific defect should be fully viable hermaphrodites, a prediction we are testing with the construction of a
dpy-27;
dpy-30::
sdc-2 XO mutant strain. How does
sdc-2 activity implement hermaphrodite differentiation and activate dosage compensation? Recently, antibodies specific to SDC-2 have revealed that SDC-2, like the dosage compensation proteins SDC-3, DPY-26 and DPY-27, is specifically localized to the X chromosomes of XX animals early in embryogenesis. In contrast, SDC-2 is not detected in XO embryos by in situ antibody staining. Preliminary evidence indicates that SDC-2 and SDC-3 associate with one another in vivo, suggesting that these two proteins may act together to recruit a dosage compensation complex to the X chromosome (see abstract by T. Davis.) In an effort to characterize the way in which the dosage compensation machinery is assembled, we are currently investigating the genetic requirements for the localization of SDC-2 to the X chromosome. In addition, we are using a biochemical approach to identify members of the dosage compensation machinery with which SDC-2 associates in vivo.