THE NEUROGENIC GENES EGGHEAD AND BRAINIAC DEFINE A NOVEL SIGNALING PATHWAY ESSENTIAL FOR EPITHELIAL MORPHOGENESIS DURING DROSOPHILA OOGENESIS

Notch (N) and other neurogenic genes have been implicated in two funda mental processes, lateral specification of cell fates, and epithelial development, Previous studies have suggested that the neurogenic gene brainiac (brn) is specifically required for epithelial development (Go ode, S., Morgan, M., Liang, Y-P. and Mahowald, A. P. (1996), Dev. Biol . 178, 35-50). In this report we show that egghead (egh), a gene with phenotypes identical to brit, encodes for a novel, putative secreted o r transmembrane protein, We describe the role of egh and brn germline function in the morphogenesis of the follicular epithelium from the ti me it is born through the time that it migrates towards the oocyte lat e in oogenesis. By comparing the function of germline egh and brn to N during oogenesis, we have obtained direct evidence for the involvemen t of Notch in maintenance of the follicle cell epithelium, and the spe cificity of brn and egh in epithelial development during oogenesis, Th e most striking phenotype observed for all three genes is a loss of ap ical-basal polarity and accumulation of follicular epithelial cells in multiple layers around the oocyte, The spatiotemporal onset of this a denoma-like phenotype correlates with the differential accumulation of egh transcripts in the oocyte at stage 4 of oogenesis. In contrast to N, we find that brn and egh are essential for the organization, but n ot specification, of stalk and polar cells. The expression patterns an d functional requirements of brit, egh, and N lead us to propose that these genes mediate follicular morphogenesis by regulating germline-fo llicle cell adhesion, This proposal offers explanations for (1) the in volvement of egh and brn in N-mediated epithelial development, but not lateral specification, (2) why brn and egh embryonic neurogenic pheno types are not as severe as N phenotypes, and (3) how egh and brn influ ence Egfr-mediated processes. The correlation between the differential expression of egh in the oocyte and the differential requirement for brit, egh, and N in maintaining the follicular epithelium around the o ocyte, suggests that Egghead is a critical component of a differential oocyte-follicle cell adhesive system.