Journal of Cell Science 115, e2301-e2301 (2002)
Copyright © 2002 The Company of Biologists Limited
Hedgehog pedals the cell cycle
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 vertebrate Hedgehog
receptor PTC1 directly interacts with and sequesters the G2/M-controlling
cyclin, cyclin B1. Hedgehog signalling could therefore promote M-phase
progression as well — by liberating PTC-bound cyclin B1.
Related articles in JCS:
- Hedgehogs tryst with the cell cycle
- Sudipto Roy and Philip W. Ingham
JCS 2002 115: 4393-4397.
[Abstract]
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