Regulation of neurogenesis and EGFR signalling by the insulin receptor/TOR pathway in Drosophila

Determining how growth and differentiation are coordinated is key to understanding normal development, as well as disease states such as cancer, where that control is lost. We have previously shown that growth and neuronal differentiation are coordinated by the insulin receptor/TOR kinase (InR/TOR) pathway. Here we show that the control of growth and differentiation diverge downstream of TOR. TOR regulates growth by controlling the activity of S6 kinase (S6K) and eIF4E. Loss of s6k delays differentiation, and is epistatic to the loss of tsc2, indicating that S6K acts downstream or in parallel to TOR in differentiation as in growth. However, loss of eIF4E does not affect the timing of differentiation. We also show, for the first time in Drosophila, that there is cross-talk between the InR/TOR pathway and epidermal growth factor receptor (EGFR) signalling. InR/TOR signalling regulates the expression of several EGFR pathway components including pointedP2 (pntP2). In addition, reduction of EGFR signalling levels phenocopies inhibition of the InR/TOR pathway in the regulation of differentiation. Together these data suggest that InR/TOR signalling regulates the timing of differentiation through modulation of EGFR target genes in developing photoreceptors.

Key Words: Drosophila, EGFR, TOR, insulin, neurogenesis

Online ISS 1091-6490
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