title: Endothelial cell-derived bone morphogenetic proteins control proliferation of neural stem/progenitor cells.
abstract: Neurogenesis persists in the adult brain subventricular zone where neural stem/progenitor cells (NSPCs) lie close to brain endothelial cells (BECs). We show in mouse that BECs produce bone morphogenetic proteins (BMPs). Coculture of embryonic and adult NSPCs with BECs activated the canonical BMP/Smad pathway and reduced their proliferation. We demonstrate that coculture with BECs in the presence of EGF and FGF2 induced a reversible cell cycle exit of NSPCs (LeX+) and an increase in the amount of GFAP/LeX-expressing progenitors thought to be stem cells. Levels of the phosphatidylinositol phosphatase PTEN were upregulated in NSPCs after coculture with BECs, or treatment with recombinant BMP4, with a concomitant reduction in Akt phosphorylation. Silencing Smad5 with siRNA or treatment with Noggin, a BMP antagonist, demonstrated that upregulation of PTEN in NSPCs required BMP/Smad signaling and that this pathway regulated cell cycle exit of NSPCs. Therefore, BECs may provide a feedback mechanism to control the proliferation of NSPCs.
authors.affiliation: CEA, DSV, iRCM, SCSR, Laboratoire de Radiopathologie-IPSC, Fontenay-aux-Roses, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Mathieu
authors.forename: Karine
authors.initials: K
authors.lastname: Sii-Felice
authors.forename: Pierre
authors.initials: P
authors.lastname: Fouchet
authors.forename: Olivier
authors.initials: O
authors.lastname: Etienne
authors.forename: Céline
authors.initials: C
authors.lastname: Haton
authors.forename: Aloïse
authors.initials: A
authors.lastname: Mabondzo
authors.forename: François D
authors.initials: FD
authors.lastname: Boussin
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Mouthon
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins