Fibroblast growth factor–hedgehog interdependence during retina regeneration
Article first published online: 26 MAR 2007
Copyright © 2007 Wiley-Liss, Inc.
Volume 236, Issue 5, pages 1161–1174, May 2007
How to Cite
Spence, J. R., Aycinena, J.-C. and Del Rio-Tsonis, K. (2007), Fibroblast growth factor–hedgehog interdependence during retina regeneration. Dev. Dyn., 236: 1161–1174. doi: 10.1002/dvdy.21115
- Issue published online: 17 APR 2007
- Article first published online: 26 MAR 2007
- Manuscript Accepted: 1 FEB 2007
- National Institutes of Health. Grant Number: EY 014197
- retina regeneration;
- sonic hedgehog;
- stem cell;
- progenitor cell
The embryonic chick is able to regenerate the retina after it has been removed. We have previously shown that proliferating stem/progenitor cells present in the ciliary body/ciliary marginal zone (CB/CMZ) of the chick eye are responsible for regeneration, which can be induced by ectopic fibroblast growth factor-2 (FGF2) or Sonic hedgehog (Shh). Here, we reveal the mechanisms showing how FGF2 and Shh signaling are interdependent during retina regeneration. If the FGF pathway is inhibited, regeneration stimulated by Shh is inhibited. Likewise, if the Hedgehog pathway is inhibited, regeneration stimulated by FGF2 is inhibited. We examined early signaling events in the CB/CMZ and found that FGF2 or Shh induced a robust Erk phosphorylation during the early stages of retina regeneration. Shh also up-regulated the expression of several members of the FGF signaling pathway. We show that ectopic FGF2 or Shh overexpression increased the number of phosphohistone 3 (PH3)-positive cells in the CB/CMZ and inhibition of either pathway decreased the number of PH3-positive cells. Additionally, both FGF and Hh signaling are required for cell survival in the CB/CMZ, whereas Hh and not FGF signaling plays a role in maintaining the identity of the retinal progenitor population in this region. Combined, our results support a model where the FGF and Hedgehog pathways work together to stimulate retina regeneration. Developmental Dynamics 236:1161–1174, 2007. © 2007 Wiley-Liss, Inc.