Proneural genetic programs include genes required for asymmetric cell division in Drosophila

In 1975 Antonio Garcia-Bellido proposed that selector genes such as the homeotic transcription factors do not themselves participate in the differentiation of the body segments they specify but instead activate (or select) a set of downstream 'realisator' genes that encode the proteins that carry out cell differentiation (Garcia-Bellido, 1975). Since then numerous genetic and molecular studies of development have borne out this view.; The proneural transcription factors act as selector genes to specify neural cell types in the ectoderm. I have taken a systematic genomics approach to discover the set of realisator genes activated by the proneural transcription factors (proneural genetic program) in the developing peripheral nervous system. This approach has led to the discovery of 30 new genes expressed specifically in the sensory organ anlagen (proneural clusters and sensory organ precursors). These new genes encode a diverse array of implied protein functions many of which are novel and unexpected. By analyzing how these new genes are regulated I have discovered a new type of regulatory module directly regulated by the proneural factors that drives expression throughout the proneural cluster. I have also begun a genetic analysis of the proneural genetic program by studying the function of the sensory organ precursor gene insensitive. insensitive encodes a conserved nuclear protein that is required for asymmetric cell division during peripheral nervous system development. Further analysis has demonstrated that insensitive contributes to Notch signaling repression in the sensory organ lineage by regulating the expression of the lethal (2) giant larvae gene. This research has revealed that the proneural transcription factors activate a diverse program of gene expression that includes newly discovered genetic functions important for both the early specification of the sensory organ precursor and later cell fate decisions in the sensory organ lineage.