Genetic and Molecular Analysis of the Mechanisms by which TSC Regulates Neuronal Differentiation

摘要

Loss of TSC pathway components alters the timing of neuronal differentiation in the Drosophila eye and wing imaginal disc. To determine the mechanisms underlying this regulation of neuronal differentiation, we have 1) further defined the subtypes of photoreceptors that respond to loss of TSC, 2) tested candidates for the regulation of differentiation in the eye, Our data indicate that loss of TSC does not control neural differentiation through 5' TOP elements contained in the mRNA of proneural genes examined (CG11799, echinoid, moleskin, src). Consistent with this conclusion, our genetic analysis ofthe Drosophila homolog of polypyrimidine tract binding protein, Hephaestus, indicates that loss of Hephaestus does not alter the timing of differentiation of photoreceptors in the eye. We conclude therefore that alternate mechanisms control this process. Our epistasis analysis indicates that S6K is essential for the precocious differentiation seen in TSC clones, while loss of eIF4E does not affect the timing of differentiation. The Ecdysone receptor (Ecr) pathway also regulates the timing of differentiation in the eye. Our genetic analysis indicates that EcR functions in a parallel pathway to TSC in the timing of differentiation.