Mechanisms underlying neural cell fate specification in the Drosophila sensory organ precursor lineage.

摘要

The sensory organ precursor (SOP) lineage is an excellent model system in which to study the molecular mechanisms that coordinate cell fate decisions in the developing Drosophila melanogaster peripheral nervous system. I have used the SOP lineage to search for genes that influence the determination of the hair, socket, neuron, and glial cells that comprise the external sensory (ES) organs in the adult fly. The SOP and all of its progeny cells require Notch signaling to be properly specified. We systematically tested the effects of gene misexpression on Notch mediated cell fate specification in the SOP lineage using a misexpression screen. I characterized two of the genes that exhibit misexpression phenotypes consistent with defects in Notch pathway signaling. tribbles misexpression causes cell fate transformations within the lineage, producing extra neurons at the expense of hair and socket cells. bantam misexpression results in the tufting of sensory bristles, perhaps by disrupting Notch pathway mediated lateral inhibition during selection of the SOP. Using loss-of-function analysis, we demonstrated that lethal giant larvae (lgl) is required for the specification of neurons and glia in the SOP lineage. Furthermore, we found that lgl acts genetically upstream of Notch and downstream of numb, suggesting a direct function for Lgl in the Numb-mediated inhibition of Notch signaling activity. Lgl is a tumor suppressor essential for the establishment and maintenance of cell polarity in epithelial cells in both Drosophila and mammalian cells. The discovery that Lgl influences Notch pathway signaling suggests that this might be a general mechanism for the coordination of cell polarity, cell fate, and proliferation.