Retinal ganglion cell-derived sonic hedgehog signaling is required for optic disc and stalk neuroepithelial cell development.
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.
Dakubo
Gabriel D
GD
Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.
Wang
Ya Ping
YP
Mazerolle
Chantal
C
Campsall
Katrina
K
McMahon
Andrew P
AP
Wallace
Valerie A
VA
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D015415:Biomarkers; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D046508:Culture Techniques; D005123:Eye / Q000196:embryology* / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D009900:Optic Nerve / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D000072079:Patched Receptors; D010641:Phenotype; D010858:Pigmentation / Q000502:physiology; D011956:Receptors, Cell Surface; D012160:Retina / Q000166:cytology / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
D015415:Biomarkers; D053823:Hedgehog Proteins; D008565:Membrane Proteins; D015513:Oncogene Proteins; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1