Hedgehog proteins are secreted signalling molecules that play crucial roles in pattern formation during early embryonic and post-embryonic development. Hedgehog signalling has a profound effect on cell fate but can also stimulate cell proliferation in certain developmental contexts — for example,during development of the cerebellum, Sonic hedgehog released by Purkinje neurons stimulates proliferation of cerebellar granule neuron precursors(CGNPs). In a Commentary on p. 4393, Sudipto Roy and Philip Ingham discuss the molecular mechanisms underlying control of the cell cycle by Hedgehog proteins. Studies of primary CGNP cultures, knockout work and gene expression profiling indicate that Hedgehog signalling can stimulate synthesis of D-type cyclins, which inactivate the tumour suppressor RB and thereby promote S phase entry. Genetic analysis of the `second mitotic wave' during fly eye development has revealed that Hedgehog can similarly induce expression of cyclin E, which also targets RB. An interesting twist is the observation that the...

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