title: Vascular endothelial growth factor signaling affects both angiogenesis and osteogenesis during the development of scleral ossicles.
abstract: Intramembranous ossification is a complex multi-step process which relies on extensive interactions among bone cells and surrounding tissues. The embryonic vasculature is essential in regulating endochondral ossification; however, its role during intramembranous ossification remains poorly understood, and in vivo studies are lacking. Previous research from our lab on the development of the intramembranous scleral ossicles has demonstrated an intriguing pattern of vascular development in which the areas of future osteogenesis remain avascular until after bone induction has occurred. Such avascular zones are located directly beneath each of the conjunctival papillae, epithelial structures which provide osteogenic signals to the underlying mesenchyme. Here we provide a high-resolution map of the developing vasculature from the time of ossicle induction to mineralization using a novel technique. We show that vegfa is expressed by the papillae and nearby mesenchymal tissue throughout HH 34-37, when vascular growth is taking place, and is down-regulated thereafter. Localized inhibition of Vegf results in expansion of the avascular zone surrounding the implanted papilla and mispatterning of the scleral ossicles. These results demonstrate that Vegf signaling could provide important insights into the complex relationship between bone and vasculature during intramembranous bone development.
authors.affiliation: Department of Medical Neuroscience, Dalhousie University, 5850 College Street, Halifax, NS, Canada B3H 4R2.
authors.forename: James
authors.initials: J
authors.lastname: Jabalee
authors.affiliation: Department of Biology, Mount Saint Vincent University, 166 Bedford Highway, Halifax, NS, Canada B3M 2J6. Electronic address: Tamara.Franz-Odendaal@msvu.ca.
authors.forename: Tamara A
authors.initials: TA
authors.lastname: Franz-Odendaal
mesh_terms: D000818:Animals; D001842:Bone and Bones; D002113:Calcification, Physiologic / Q000502:physiology; D002642:Chick Embryo; D004429:Ear Ossicles / Q000098:blood supply / Q000196:embryology*; D004730:Endothelium, Vascular / Q000196:embryology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009898:Optic Disk / Q000098:blood supply / Q000196:embryology; D010012:Osteogenesis / Q000502:physiology*; D012590:Sclera / Q000098:blood supply / Q000196:embryology*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A
keywords: Bone; Eye; Intramembranous ossification; Sclera; Scleral ossicles; Sclerotic ring; Skeleton; Vasculature; Vegf