Editors' ChoiceDevelopment

Integrating Growth with Developmental Timing

Science's STKE  12 Oct 2004:
Vol. 2004, Issue 254, pp. tw361
DOI: 10.1126/stke.2542004tw361

During development, temporal and spatial cues control cell fate and tissue organization. Using a screen for mutations that cause patterning defects in the Drosophila eye, Bateman and McNeill identified the gene encoding tuberous sclerosis complex 1 (TSC1). Further analysis of the patterning defect indicated that the organization was disrupted by premature differentiation of the photoreceptor cells, leading to overrotation of the ommatidia. The secretion of the epidermal growth factor ligand spitz, which activates a known pathway involved in photoreceptor differentiation, was apparently normal in tsc–/– cells, because they and wild-type cells had similar amounts of phosphorylated extracellular signal-regulated kinase (ERK) and of various downstream components. Premature acquisition of differentiation markers was also observed with a mutation that inactivated the phosphatase PTEN, which like TSC1 is a negative regulator of the pathways controlled by TOR and the insulin receptor. Analysis of the ommatidial differentiation timing in cells carrying mutations that disrupted signaling through the insulin receptor pathway revealed delayed photoreceptor differentiation, whereas excessive activation of the pathway produced precocious differentiation. Similar alterations in developmental timing were noted for the peripheral sensory organ, the chorodontal organ, but not for hair formation in the pupal wing. The change in timing did not appear to be a consequence of a change in the size of the cells, because overexpression of Myc or cyclin D and cyclin-dependent kinase 4 (CDK4) did not produce the same patterning defects. Thus, the pathways that regulate growth also appear to contribute to developmental timing, providing a mechanism for coordination of development with nutritional status.

J. M. Bateman, H. McNeill, Temporal control of differentiation by the insulin receptor/Tor pathway in Drosophila. Cell 119, 87-96 (2004). [Online Journal]