Cell fate induction and programmed cell death in the Drosophila pupal retina

This dissertation explores patterning, programmed cell death, and cell fate induction in a developing neuroepithelium, the Drosophila pupal retina. Patterning events, including PCD, depend upon the coordination of multiple signaling pathways. The nature of such signals, however, is poorly understood. Direct ablation with a UV laser revealed the source and position of two signals required for regulating the pattern of PCD among interommatidial cells of the Drosophila retina. Within the interommatidial lattice, Notch-mediated signals shared among uncommitted cells result in removal of unneeded cells through PCD. In addition, an adjacent pigment cell imposes pattern on its uncommitted neighbors by providing a 'life'-promoting signal to the lattice; evidence is provided that this signal occurs through localized, Spitz-mediated activation of the EGF Receptor/Ras pathway. Together, these signals achieve the highly regulated pattern observed in the adult retina.; In order to identify novel genes that are potentially involved in patterning the pupal retina, 3000 beta-galactosidase-expressing enhancer trap fly lines were screened for their pupal eye expression pattern. The BEO2 line expresses a beta-galactosidase reporter broadly in undifferentiated eye cells, and then more specifically in just the primary pigment cells and adjacent cone cells. Laser ablation of the cone cells has demonstrated that these cells induce primary pigment cell differentiation, suggesting that the gene identified by BEO2 may be involved in specification of the primary pigment cell fate. Cloning of the genomic locus surrounding the BEO2 insert has identified a pair of novel cytoplasmic protein tyrosine phosphatases. Excision of the BEO2 insert leads to embryonic lethality, suggesting a fundamental role of these phosphatases in development. Overexpression of the wild type phosphatase Primo-2 results in occasional extra primary pigment cells, alluding to a role for these phosphatases in cell fate specification of primary pigment cells. Overexpression of a dominant-interfering form of the same enzyme may provide more insight into the signaling pathways which interact with these novel tyrosine phosphatases.