title: Critical time window of hedgehog-dependent angiogenesis in murine yolk sac.
abstract: Hedgehog family was reported to be involved in murine yolk sac angiogenesis. However, it has not been clarified whether impaired angiogenesis under hedgehog signaling blockade is attributable to true defect in angiogenic process or just a sequel of earlier vasculogenic abnormalities. In the present study, we examined the effects of stage-specific inhibition of hedgehog cascade on vascular morphogenesis by applying cyclopamine or jervine to culture media of whole embryo culture system from embryonic days 8.0 until 9.5. Whole-mount immunostaining revealed that cyclopamine or jervine treatment in a narrow time window impaired angiogenic remodeling such as ramification into large and small branches and pericyte recruitment, although vasculogenesis was grossly normal. Molecular analyses suggest that indian hedgehog in the yolk sac endoderm regulates the induction of VEGF, Flk-1 and Notch-1. Our results indicate that hedgehog signaling is indispensable for mouse yolk sac angiogenesis, even when vasculogenesis is not perturbed.
authors.affiliation: Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. mnagase-tky@umin.ac.jp
authors.forename: Miki
authors.initials: M
authors.lastname: Nagase
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagase
authors.forename: Isao
authors.initials: I
authors.lastname: Koshima
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism; D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D003470:Culture Media / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D042787:Receptor, TIE-2 / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014704:Veratrum Alkaloids / Q000494:pharmacology; D015017:Yolk Sac / Q000098:blood supply* / Q000254:growth & development / Q000502:physiology
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D003470:Culture Media; D053823:Hedgehog Proteins; D015534:Trans-Activators; D014704:Veratrum Alkaloids; C010206:jervine; D042787:Receptor, TIE-2; C000541:cyclopamine