Activin signaling limits the competence for retinal regeneration from the pigmented epithelium.
Regeneration of the retina in amphibians is initiated by the transdifferentiation of the retinal pigmented epithelium (RPE) into neural progenitors. A similar process occurs in the early embryonic chick, but the RPE soon loses this ability. The factors that limit the competence of RPE cells to regenerate neural retina are not understood; however, factors normally involved in the development of the eye (i.e. FGF and Pax6) have also been implicated in transdifferentiation. Therefore, we tested whether activin, a TGFbeta family signaling protein shown to be important in RPE development, contributes to the loss in competence of the RPE to regenerate retina. We have found that addition of activin blocks regeneration from the RPE, even during stages when the cells are competent. Conversely, a small molecule inhibitor of the activin/TGFbeta/nodal receptors can delay, and even reverse, the developmental restriction in FGF-stimulated neural retinal regeneration.
Department of Biological Structure, 357420 Health Science Center, University of Washington, School of Medicine, Seattle, WA 98195, USA.
Sanae
S
Sakami
Paige
P
Etter
Thomas A
TA
Reh
D028341:Activins / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation; D002642:Chick Embryo; D004149:Dioxoles / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016133:Polymerase Chain Reaction; D015398:Signal Transduction
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D016222:Fibroblast Growth Factor 2; D028341:Activins