title: BMP9 and BMP10 are critical for postnatal retinal vascular remodeling.
abstract: ALK1 is a type I receptor of the TGF-β family that is involved in angiogenesis. Circulating BMP9 was identified as a specific ligand for ALK1 inducing vascular quiescence. In this work, we found that blocking BMP9 with a neutralizing antibody in newborn mice significantly increased retinal vascular density. Surprisingly, Bmp9-KO mice did not show any defect in retinal vascularization. However, injection of the extracellular domain of ALK1 impaired retinal vascularization in Bmp9-KO mice, implicating another ligand for ALK1. Interestingly, we detected a high level of circulating BMP10 in WT and Bmp9-KO pups. Further, we found that injection of a neutralizing anti-BMP10 antibody to Bmp9-KO pups reduced retinal vascular expansion and increased vascular density, whereas injection of this antibody to WT pups did not affect the retinal vasculature. These data suggested that BMP9 and BMP10 are important in postnatal vascular remodeling of the retina and that BMP10 can substitute for BMP9. In vitro stimulation of endothelial cells by BMP9 and BMP10 increased the expression of genes involved in the Notch signaling pathway (Jagged1, Dll4, Hey1, Hey2, Hes1) and decreased apelin expression, suggesting a possible cross-talk between these pathways and the BMP pathway.
authors.affiliation: INSERM U1036, 17 rue des Martyrs, Grenoble, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ricard
authors.forename: Delphine
authors.initials: D
authors.lastname: Ciais
authors.forename: Sandrine
authors.initials: S
authors.lastname: Levet
authors.forename: Mariela
authors.initials: M
authors.lastname: Subileau
authors.forename: Christine
authors.initials: C
authors.lastname: Mallet
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Zimmers
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Marie
authors.initials: M
authors.lastname: Bidart
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Feige
authors.forename: Sabine
authors.initials: S
authors.lastname: Bailly
mesh_terms: D030201:Activin Receptors, Type I / Q000737:chemistry / Q000494:pharmacology; D030301:Activin Receptors, Type II; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002452:Cell Count; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D055427:Growth Differentiation Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000494:pharmacology; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D000906:Antibodies; C119152:Bmp10 protein, mouse; D019485:Bone Morphogenetic Proteins; C526108:Gdf2 protein, mouse; D055427:Growth Differentiation Factor 2; D011994:Recombinant Proteins; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; C498931:Acvrl1 protein, mouse