brainiac (brn) is involved in a number of developmental events. In addition 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. Animals harboring strong mutations of either grk or EGF receptor tyrosine kinase (Egfr) or doubly mutant for brn and weak grk or Egfr mutations produce ovarian follicles with multiple sets of nurse cell-oocyte complexes. These follicles frequently have discontinuities in the follicular epithelium that uncover nurse cells but not the oocyte. Gaps first appear in the germarium, suggesting that some nurse cells lack affinity for invading prefollicular cells. This is the first evidence that grk, in addition to its involvement in the genesis of anterior-posterior and dorsal-ventral polarity, is also required for Egfr-dependent development of the follicular epithelium that surrounds each nurse cell/oocyte cluster to form an egg chamber. We have used restriction fragment length polymorphisms to localize brn 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. brn codes for a putative secreted protein. brn is expressed in germ cells at the time follicle cells first surround the nurse cell-oocyte complex. Our genetic data suggest that brn acts in a parallel, but partially overlapping pathway to the Grk-Egfr signaling pathway. The brn pathway may help to provide specificity to TGF alpha -Egfr function during oogenesis.