title: Indian hedgehog signaling from endothelial cells is required for sclera and retinal pigment epithelium development in the mouse eye.
abstract: The development of extraocular orbital structures, in particular the choroid and sclera, is regulated by a complex series of interactions between neuroectoderm, neural crest and mesoderm derivatives, although in many instances the signals that mediate these interactions are not known. In this study we have investigated the function of Indian hedgehog (Ihh) in the developing mammalian eye. We show that Ihh is expressed in a population of non-pigmented cells located in the developing choroid adjacent to the RPE. The analysis of Hh mutant mice demonstrates that the RPE and developing scleral mesenchyme are direct targets of Ihh signaling and that Ihh is required for the normal pigmentation pattern of the RPE and the condensation of mesenchymal cells to form the sclera. Our findings also indicate that Ihh signals indirectly to promote proliferation and photoreceptor specification in the neural retina. This study identifies Ihh as a novel choroid-derived signal that regulates RPE, sclera and neural retina development.
authors.affiliation: University of Ottawa Eye Institute, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5.
authors.forename: Gabriel D
authors.initials: GD
authors.lastname: Dakubo
authors.forename: Chantal
authors.initials: C
authors.lastname: Mazerolle
authors.forename: Marosh
authors.initials: M
authors.lastname: Furimsky
authors.forename: Chuan
authors.initials: C
authors.lastname: Yu
authors.forename: Benoit
authors.initials: B
authors.lastname: St-Jacques
authors.forename: Andrew P
authors.initials: AP
authors.lastname: McMahon
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Wallace
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002829:Choroid / Q000196:embryology; D042783:Endothelial Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D017496:Hypopigmentation / Q000473:pathology; D051741:Kruppel-Like Transcription Factors; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009915:Orbit / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000002:abnormalities / Q000196:embryology* / Q000648:ultrastructure; D012160:Retina / Q000196:embryology / Q000473:pathology; D012590:Sclera / Q000002:abnormalities / Q000196:embryology* / Q000648:ultrastructure; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: D015415:Biomarkers; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; C465570:Shh protein, mouse; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1; C109288:cone rod homeobox protein; C514061:ihh protein, mouse