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Shh directs cell‐cycle exit by activating p57Kip2 in the zebrafish retina
Author(s) -
Shkumatava Alena,
Neumann Carl J
Publication year - 2005
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400416
Subject(s) - microbiology and biotechnology , zebrafish , cell cycle , sonic hedgehog , biology , hedgehog signaling pathway , hedgehog , cell , cell cycle protein , retina , signal transduction , genetics , neuroscience , gene
The Hedgehog (Hh) family of signalling proteins control both differentiation and proliferation during animal development. Previous studies have shown that Hh signalling has a stimulatory effect on the cell cycle in several organs by controlling core cell‐cycle components. Here, we show that Sonic hedgehog (Shh) signalling has the opposite effect in the zebrafish retina, where it leads to cell‐cycle exit, and that this is mediated by transcriptional activation of the cyclin kinase inhibitor p57Kip2. The loss of p57Kip2 activity strongly resembles the Shh mutant eye phenotype, and overexpression of p57Kip2 rescues cell‐cycle exit in Shh mutants, indicating that p57Kip2 is both necessary and sufficient to mediate Shh‐induced cell‐cycle exit in the retina. These findings raise the possibility that stimulation of cell‐cycle exit through regulation of core cell‐cycle components may be part of a general mechanism required for Hh‐directed differentiation.