BRAINIAC ENCODES A NOVEL, PUTATIVE SECRETED PROTEIN THAT COOPERATES WITH GRK TGF-ALPHA IN THE GENESIS OF THE FOLLICULAR EPITHELIUM

brainiac (bm) is involved in a number of developmental events. In addi tion to being required zygotically for segregation of neuroblasts from epidermoblasts, it is essential for a series of critical steps during oogenesis which also depend upon gurken (grk) a TGF alpha homolog. An imals harboring strong mutations of either grk or EGF receptor tyrosin e kinase (Egfr) or doubly mutant for brn and weak grk or Egfr mutation s produce ovarian follicles with multiple sets of nurse cell-oocyte co mplexes. These follicles frequently have discontinuities in the follic ular epithelium that uncover nurse cells but not the oocyte. Gaps firs t appear in the germarium, suggesting that some nurse cells lack affin ity for invading prefollicular cells. This is the first evidence that grk, in addition to its involvement in the genesis of anterior-posteri or and dorsal-ventral polarity, is also required for Egfr-dependent de velopment of the follicular epithelium that surrounds each nurse cell/ oocyte cluster to form an egg chamber. We have used restriction fragme nt length polymorphisms to localize bm to a 10-kb region within a 300- kb stretch of DNA on the X-chromosome, and we have identified the brn gene by means of RNA rescue. bm codes for a putative secreted protein. bm is expressed in germ cells at the time follicle cells first surrou nd the nurse cell-oocyte complex. Our genetic data suggest that bm act s in a parallel, but partially overlapping pathway to the Grk-Egfr sig naling pathway. The brn pathway may help to provide specificity to TGF alpha-Egfr function during oogenesis. (C) 1996 Academic Press, Inc.