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Perspectives

A General Role of Hedgehog in the Regulation of Proliferation

Michalis Agathocleous, Morgane Locker, William A. Harris and Muriel Perron

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The Hedgehog (Hh) pathway regulates proliferation in a variety of tissues, however its specific effects on the cell cycle are unclear. During retinal proliferation in particular, the role of Hh has been controversial, with studies variably suggesting a stimulatory or an inhibitory effect on proliferation. Our recent data provide an underlying mechanism, which reconciles these different views. We showed that Hh signaling in the retina accelerates the G1 and G2 phases of the cell cycle and then pushes these rapidly dividing cells out of the cell cycle prematurely. From this and other evidence, we propose that Hh converts quiescent retinal stem cells into fast-cycling transient amplifying progenitors that are closer to cell cycle exit and differentiation. This is, we suggest, likely to be a general role of Hh in the nervous system and other tissues. This function of Hh in cell cycle kinetics and cell cycle exit may have implications for tumorigenesis and brain evolution.

Authors

Michalis Agathocleous

Cambridge University; Cambridge, UK

Morgane Locker

Univ Paris Sud; UMR CNRS 8080; Orsay, France

William A. Harris

Cambridge University; Cambridge, UK

Muriel Perron

Univ Paris Sud; UMR CNRS 8080; Orsay, France

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.