Regulation of neurogenesis and epidermal growth factor receptor signaling by the insulin receptor/target of rapamycin 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/target of rapamycin (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 inhibits growth but does not affect the timing of differentiation. We also show, for the first time in Drosophila, that there is crosstalk between the InR/TOR pathway and epidermal growth factor receptor (EGFR) signaling. InR/TOR signaling regulates the expression of several EGFR pathway components including pointedP2 (pntP2). In addition, reduction of EGFR signaling levels phenocopies inhibition of the InR/TOR pathway in the regulation of differentiation. Together these data suggest that InR/TOR signaling regulates the timing of differentiation through modulation of EGFR target genes in developing photoreceptors.
McNeill
Helen
H
The Wolfson Centre For Age-Related Diseases, King's College, London SE1 1UL, United Kingdom.
Craig
Gavin M
GM
Bateman
Joseph M
JM
D000818:Animals; D030801:Animals, Genetically Modified; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004843:Epistasis, Genetic; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology; D017344:Genes, Insect; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000502:physiology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology*; D017956:Photoreceptor Cells, Invertebrate / Q000254:growth & development / Q000502:physiology; D011494:Protein Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D000076205:Ras Homolog Enriched in Brain Protein; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000254:growth & development / Q000502:physiology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D066246:ErbB Receptors; D005136:Eye Proteins; D020559:Monomeric GTP-Binding Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D011518:Proto-Oncogene Proteins; D000076205:Ras Homolog Enriched in Brain Protein; D011972:Receptor, Insulin; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; C490212:Rheb protein, Drosophila; C083884:pnt protein, Drosophila; C075638:aos protein, Drosophila; C416303:target of rapamycin protein, Drosophila