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doi: 10.1242/10.1242/dev.00515


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Development 130, 2967-2980 (2003)
Copyright © 2003 The Company of Biologists Limited

Retinal ganglion cell-derived sonic hedgehog signaling is required for optic disc and stalk neuroepithelial cell development

Gabriel D. Dakubo1, Ya Ping Wang1, Chantal Mazerolle1, Katrina Campsall1, Andrew P. McMahon2 and Valerie A. Wallace1,3,*

1 Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada
2 Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
3 Eye Institute, Center for Neuromuscular Disease, and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada

* Author for correspondence (e-mail: vwallace{at}ohri.ca)

Accepted 31 March 2003

The development of optic stalk neuroepithelial cells depends on Hedgehog (Hh) signaling, yet the source(s) of Hh protein in the optic stalk is unknown. We provide genetic evidence that sonic hedgehog (Shh) from retinal ganglion cells (RGCs) promotes the development of optic disc and stalk neuroepithelial cells. We demonstrate that RGCs express Shh soon after differentiation, and cells at the optic disc in close proximity to the Shh-expressing RGCs upregulate Hh target genes, which suggests they are responding to RGC-derived Shh signaling. Conditional ablation of Shh in RGCs caused a complete loss of optic disc astrocyte precursor cells, resulting in defective axon guidance in the retina, as well as conversion of the neuroepithelial cells in the optic stalk to pigmented cells. We further show that Shh signaling modulates the size of the Pax2+ astrocyte precursor cell population at the optic disc in vitro. Together, these data provide a novel insight into the source of Hh that promotes neuroepithelial cell development in the mammalian optic disc and stalk.

Key words: Retinal ganglion cells, Shh, Ihh, Pax2, Optic disc/stalk, Neuroepithelial cells, Astrocyte precursor cells, Development, Mouse




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