Primary Sex Determination in Drosophila melanogaster Does Not Rely on the Male-Specific Lethal Complex

It has been proposed that the Male Specific Lethal (MSL) complex is active in Drosophila melanogaster embryos of both sexes prior to the maternal-to-zygotic transition. Elevated gene expression from the two X chromosomes of female embryos is proposed to facilitate the stable establishment of Sex-lethal (Sxl) expression, which determines sex and represses further activity of the MSL complex, leaving it active only in males. Important supporting data included female-lethal genetic interactions between the seven msl genes and either Sxl or scute and sisterlessA, two of the X-signal elements (XSE) that regulate early Sxl expression. Here I report contrary findings that there are no female-lethal genetic interactions between the msl genes and Sxl or its XSE regulators. Fly stocks containing the msl3(1) allele were found to exhibit a maternal-effect interaction with Sxl, scute, and sisterlessA mutations, but genetic complementation experiments showed that msl3 is neither necessary nor sufficient for the female-lethal interactions, which appear to be due to an unidentified maternal regulator of Sxl. Published data cited as evidence for an early function of the MSL complex in females, including a maternal effect of msl2, have been reevaluated and found not to support a maternal, or other effect, of the MSL complex in sex determination. These findings suggest that the MSL complex is not involved in primary sex determination or in X chromosome dosage compensation prior to the maternal-to-zygotic transition.