Snail Protein Family in Drosophila Neurogenesis: a Dissertation

Abstract

The Snail protein functions as a transcriptional regulator to establish early mesodermal cell fate in Drosophila. Later, in germ band-extended embryos, Snail is considered a pan-neural protein based on its extensive expression in neuroblasts. The evidence presented in thesis links snail expression and function in CNS. Cloning and functional characterization of a novel snail homologue, in Drosophila, are also described here. Cloning of this gene, worniu (Chinese for snail), revealed that the neural function of snail is masked by this and another closely related gene escargot. Both Escargot and Worniu contain zinc finger domains that are highly homologous to that of Snail. These three members of Snail protein family are redundantly required for CNS development. Although not affecting formation of neuroblasts, the loss of expression of these three members correlates with disruption of Nb asymmetry and division. Downstream targets of Snail protein family, in these processes, are inscuteable and string. In mutant embryos, which have the three genes deleted, the RNA expression of inscuteable and string is significantly lowered. Consistent with the gene expression defects, the mutant embryos have loss of asymmetric localization of prospero RNA in neuroblasts and nuclear localization of Prospero protein in ganglion mother cells. Transgenic expression of inscuteable and string together, in the snail family deletion mutant, efficiently restores the Prospero expression in GMC, demonstrating that the two genes are key targets of Snail in Nbs. Like in the mesoderm, in CNS Snail function depends on interaction with dCtBP co-repressor. These results suggest that Sna [Snail] family of proteins control both asymmetry and cell division of neuroblasts by activating, perhaps indirectly, the expression of inscuteable and string.