This conclusion was derived from work on a gene,
tsc1
(tuberous sclerosis complex 1), which the authors recovered in a genetic screen for fly mutants with defective planar polarity in the eye. As expected from the mutant phenotype of the vertebrate homologue of tsc1, which encodes a tumour suppressor, homozygous mutant photoreceptor cells are larger than normal, but otherwise differentiate normally. What was peculiar, however, was that several types of mutant photoreceptor cells — which are studied precisely because their differentiation is so stereotypical — differentiated more precociously than their genetically wild-type neighbours. This speeded-up development did not lead to an abnormal eye unit or to ectopic cell fates, but simply to an acceleration of the normal differentiation program.
How does wild-type tsc1 control the rate of differentiation? Mutations that activate the InR pathway cause precocious differentiation in the eye, as with mutations in tsc1. The converse experiment, in which the InR and Tor pathways were inactivated, led to delays in neuronal differentiation. This work further supports the involvement of tsc1 in InR and Tor pathways and, importantly, implicates these pathways in the control of developmental timing. The cells that make up each eye unit in the fly are recruited to their fate by reiterative signalling through the Ras/MAPK pathway; however, lack of tsc1 does not seem to affect this signalling, indicating that tsc1 acts downstream of known components of this pathway or in parallel to them.
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