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Hedgehog signaling and the retina: insights into the mechanisms controlling the proliferative properties of neural precursors

¹ Laboratoire «Gènes, Développement et Neurogenèse,» Université Paris XI, UMR Centre national de la recherche scientifique (CNRS) 8080, 91405 Orsay, France; ² Department of Physiology, Development and Neuroscience, Cambridge University, Cambridge, CB2 3DY, United Kingdom

Hedgehog signaling has been linked to cell proliferation in a variety of systems; however, its effects on the cell cycle have not been closely studied. In the vertebrate retina, Hedgehog's effects are controversial, with some reports emphasizing increased proliferation and others pointing to a role in cell cycle exit. Here we demonstrate a novel role for Hedgehog signaling in speeding up the cell cycle in the developing retina by reducing the length of G1 and G2 phases. These fast cycling cells tend to exit the cell cycle early. Conversely, retinal progenitors with blocked Hedgehog signaling cycle more slowly, with longer G1 and G2 phases, and remain in the cell cycle longer. Hedgehog may modulate cell cycle kinetics through activation of the key cell cycle activators cyclin D1, cyclin A2, cyclin B1, and cdc25C. These findings support a role for Hedgehog in regulating the conversion from slow cycling stem cells to fast cycling transient amplifying progenitors that are closer to cell cycle exit.

[Keywords: Hedgehog; retinal stem cells; Xenopus ; zebrafish; cell cycle kinetics; cell cycle exit; cyclin; Cdc25C]

Received April 18, 2006; revised version accepted September 5, 2006.

⁴ Corresponding author.

E-MAIL muriel.perron{at}ibaic.u-psud.fr; FAX 33-1-69-15-68-02.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.391106.

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