Azlan, A.; Fukunaga, R.

The self-renewal and differentiation of germline stem cells (GSCs) are tightly regulated during oogenesis. The Drosophila female germline provides a powerful model to study these regulatory mechanisms. We previously identified Sakura (also known as Bourbon/CG14545) as a crucial factor for maintenance and differentiation of GSCs and oogenesis, and demonstrated that Sakura binds to Ovarian Tumor (Otu), another essential regulator of these processes. Here, we identify MYCBP (c-Myc binding protein) as an additional essential component of this regulatory network. We show that MYCBP physically associates with itself, Sakura, and Otu, forming binary and ternary complexes including a MYCBP*Sakura*Otu complex. MYCBP is highly expressed in the ovary, and mycbp null mutant females exhibit rudimentary ovaries with germline-less and tumorous ovarioles, fail to produce eggs, and are completely sterile. Germline-specific depletion of mycbp disrupts Dpp/BMP signaling, causing aberrant expression of bag-of-marbles (bam) and leading to defective differentiation and GSC loss. In addition, mycbp is required for female-specific splicing of sex-lethal (sxl), a master regulator of sex identity determination. These phenotypes closely resemble those observed those of sakura and otu mutants. Together, our findings reveal that MYCBP functions in concert with Sakura and Otu to coordinate self-renewal and differentiation of GSCs and oogenesis in Drosophila.