sisterless Ais required for the activation ofSex lethalin the germline

InDrosophila,sex determination in somatic cells has been well-studied and is under the control of the switch geneSex lethal(Sxl), which is activated in females by the presence of two X chromosomes. Though sex determination is regulated differently in the germline versus the soma,Sxlis also necessary and sufficient for the female identity in germ cells. Loss ofSxlfunction in the germline results in ovarian germline tumors, a characteristic of male germ cells developing in a female soma. Further, XY (male) germ cells expressingSxlare able to produce eggs when transplanted into XX (female) somatic gonads, demonstrating thatSxlis also sufficient for female sexual identity in the germline. As in the soma, the presence of two X chromosomes is sufficient to activateSxlin the germline, but the mechanism for “counting” X chromosomes in the germline is thought to be different from the soma. Here we have explored this mechanism at bothcis- andtrans-levels. Our data support the model that theSxl“establishment” promoter (SxlPE) is activated in a female-specific manner in the germline, as in the soma, but that the timing ofSxlPEactivation, and the DNA elements that regulateSxlPEare different from those in the soma. Nevertheless, we find that the X chromosome-encoded genesisterless A (sisA),which helps activateSxlin the soma, is also essential forSxlactivation in the germline. Loss ofsisAfunction leads to loss of Sxl expression in the germline, and to ovarian tumors and germline loss. These defects can be rescued by the expression of Sxl, demonstrating thatsisAlies upstream ofSxlin germline sex determination. We conclude thatsisAacts as an X chromosome counting element in both the soma and the germline, but that additional factors that ensure robust, female-specific expression of Sxl in the germline remain to be discovered.