A novel function forHedgehogsignalling in retinal pigment epithelium differentiation
- 15 April 2003
- journal article
- Published by The Company of Biologists in Development
- Vol. 130 (8), 1565-1577
- https://doi.org/10.1242/dev.00391
Abstract
Sonic hedgehog is involved in eye field separation along the proximodistal axis. We show that Hh signalling continues to be important in defining aspects of the proximodistal axis as the optic vesicle and optic cup mature. We show that two other Hedgehog proteins, Banded hedgehog and Cephalic hedgehog, related to the mouse Indian hedgehog and Desert hedgehog, respectively, are strongly expressed in the central retinal pigment epithelium but excluded from the peripheral pigment epithelium surrounding the ciliary marginal zone. By contrast, downstream components of the Hedgehog signalling pathway, Gli2, Gli3 and X-Smoothened, are expressed in this narrow peripheral epithelium. We show that this zone contains cells that are in the proliferative state. This equivalent region in the adult mammalian eye, the pigmented ciliary epithelium, has been identified as a zone in which retinal stem cells reside. These data, combined with double labelling and the use of other retinal pigment epithelium markers, show that the retinal pigment epithelium of tadpole embryos has a molecularly distinct peripheral to central axis. In addition, Gli2, Gli3 and X-Smoothened are also expressed in the neural retina, in the most peripheral region of the ciliary marginal zone, where retinal stem cells are found in Xenopus, suggesting that they are good markers for retinal stem cells. To test the role of the Hedgehog pathway at different stages of retinogenesis, we activated the pathway by injecting a dominant-negative form of PKA or blocking it by treating embryos with cyclopamine. Embryos injected or treated at early stages display clear proximodistal defects in the retina. Interestingly, the main phenotype of embryos treated with cyclopamine at late stages is a severe defect in RPE differentiation. This study thus provides new insights into the role of Hedgehog signalling in the formation of the proximodistal axis of the eye and the differentiation of retinal pigment epithelium.Keywords
This publication has 69 references indexed in Scilit:
- Transdifferentiation of Pigmented Epithelial Cells: A Source of Retinal Stem Cells?Developmental Neuroscience, 2001
- Pigment epithelium‐derived factor supports normal Müller cell development and glutamine synthetase expression after removal of the retinal pigment epitheliumGlia, 2001
- Erythroid Differentiation in Vitro Is Blocked by Cyclopamine, an Inhibitor of Hedgehog SignalingBlood Cells, Molecules, and Diseases, 2000
- Identification of Neural Progenitors in the Adult Mammalian EyeBiochemical and Biophysical Research Communications, 2000
- Sonic hedgehog signaling by the Patched–Smoothened receptor complexCurrent Biology, 1999
- Inductive effects of the retinal pigmented epithelium (RPE) on histogenesis of the avian retina as revealed by retinospheroid technologySeminars in Cell & Developmental Biology, 1998
- Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene functionNature, 1996
- Patterning activities of vertebrate hedgehog proteins in the developing eye and brainCurrent Biology, 1995
- Lipofection of cDNAs in the embryonic vertebrate central nervous systemNeuron, 1990
- Cell lineage analysis reveals multipotent precursors in the ciliary margin of the frog retinaDevelopmental Biology, 1989