title: Extraretinal and retinal hedgehog signaling sequentially regulate retinal differentiation in zebrafish.
abstract: Hedgehog (Hh) signaling is required for eye development in vertebrates; known roles in the zebrafish include regulation of eye morphogenesis and ganglion cell and photoreceptor differentiation. We employed a temporally selective Hh signaling knockdown strategy, by using antisense morpholino oligonucleotides or the teratogenic alkaloid cyclopamine, in order to dissect the separate roles of Hh signaling arising from specific sources. We also examined the eye phenotype of zebrafish slow muscle-omitted (smu) mutants, which lack a functional smoothened gene, encoding a component of the Hh signal transduction pathway. We find that Hh signaling from extraretinal sources is required for the initiation of retinal differentiation, but this involvement may be independent of the effects of Hh signaling on optic stalk development. We also find that Hh signals from ganglion cells participate in propagating expression of ath5, and we suggest that the effects of Hh signals from the retinal pigmented epithelium on photoreceptor differentiation may be mediated by the transcription factor rx1.
authors.affiliation: Department of Biological Sciences, University of Idaho, Moscow, ID 83844-3051, USA. dtenkam@uidaho.edu
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Stenkamp
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Frey
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D018390:Gene Targeting; D006133:Growth Substances / Q000235:genetics / Q000502:physiology; D053823:Hedgehog Proteins; D008954:Models, Biological; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D012160:Retina / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects; D015398:Signal Transduction; D000072086:Smoothened Receptor; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D006133:Growth Substances; D053823:Hedgehog Proteins; D016376:Oligonucleotides, Antisense; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D015534:Trans-Activators; D029961:Zebrafish Proteins; C413414:atoh7 protein, zebrafish; C491021:smo protein, zebrafish