Genetic and Molecular Analysis of the Mechanisms by Which TSC Regulates Neuronal Differentiation
Annual rept. 14 Jan 2006-13 Jan 2007
MOUNT SINAI HOSPITAL TORONTO (ONTARIO)
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We have previously shown that 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 in silico candidates for the regulation of differentiation in the eye, and 3 optimized conditions for an RNAi screen. Our preliminary 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 of the Drosophilahomolog 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 preliminary epistasisanalysis indicates that S6K is essential for the precocious differentiation seen in TSC clones, while loss of eIF4E does not affect the timing of differentiation.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research