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MCNEILL/ELSEVIER
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# g6 D. e. a; W4 J# mInsulin hastens or delays differentiation so that it keeps pace with growth rates, according to results from Joseph Bateman and Helen McNeill (Cancer Research UK, London, UK).
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' O& R4 `1 L0 i, d" I/ O7 s# ]/ W4 z MInsulin is the perfect candidate to decide when cells should differentiate, as it is a well-known growth regulator. Along with the Tor pathway, which senses amino acid levels, insulin turns up ribosome synthesis to match increased nutrient availability. Bateman and McNeill now find that insulin and Tor also control neuronal tissue differentiation. Whereas the identities of cell fates were unaffected by changes in insulin signaling, the fates were acquired at inappropriate times.
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3 G1 t* Z* i/ O) v" ?" L* Z" UThe aberrant timings were easily seen in the developing fly eye, whose 800 photoreceptor clusters differentiate in a wave pattern that makes timing mutants easy to identify. While using the eye to find patterning mutants, the authors found that cells lacking TSC1, a negative regulator of Tor, differentiated prematurely compared with neighboring TSC1-containing clusters. Dampened insulin or Tor signaling, in contrast, delayed differentiation. Thus, when growth was delayed by factors resulting in low insulin levels, differentiation was also delayed appropriately.
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' ^6 T; f Y6 ?9 ^The altered timings were measured by changes in the appearance of definitive transcription factors such as Elav and Prospero. But the Ras/MAPK pathway, which turns on these transcription factors, was not affected by tsc1. As it does with ribosomal proteins, insulin signaling may activate the translation of a differentiation factor that lies downstream of or parallel to Ras/MAPK.
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Insulin's control was independent of absolute cell size, thus allowing cell types of varying sizes to time differentiation via the same mechanism. Tsc1 had no effect on differentiation timing outside the nervous system, however. Neurons may depend on this insulin system because they are particularly sensitive to timing miscues given the precision required to make distant synaptic connections.
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Reference:0 d% T4 w7 B' v
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Bateman, J.M., and H. McNeill. 2004. Cell. 119:87–96.(Cells lacking TSC1 (outlined) express El) |
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发表于 2009-3-6 08:14
发表于 2026-9-30 09:53
