title: Endothelial cell-derived bone morphogenetic proteins regulate glial differentiation of cortical progenitors.
abstract: Gliogenesis is an important component of cortical development during the postnatal period. Two macroglial cells are generated in a particular order, i.e. astrocytes first and oligodendrocytes later. The mechanisms underlying this sequence of glial differentiation are unknown but interactions with blood vessels are postulated to play a role. We show, using a mouse in-vitro coculture system, that endothelial cells promote astrocyte differentiation but inhibit oligodendrocyte differentiation of postnatal cortical progenitors. Endothelial cells produce bone morphogenetic proteins (BMPs) to activate Sma- and Mad-related protein (Smad) signalling in progenitors and the effects of endothelial cells on glial differentiation are blocked by the BMP antagonist Noggin. Differentiation of progenitors into astrocytes results in the inhibition of endothelial cell growth, accompanied by changes in gene expression of angiogenic factors, indicating bidirectional interactions between progenitors and endothelial cells. In vivo, Smad signalling is activated in various types of cortical cells including progenitors in association with astrogenesis but is inactivated before the peak of oligodendrogenesis. Capillary vessels isolated from the developing cortex express high levels of BMPs. Together, these results demonstrate that endothelial cells regulate glial differentiation by secreting BMPs in vitro and suggest a similar role in cortical gliogenesis in vivo.
authors.affiliation: Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. timura@koto.kpu-m.ac.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Imura
authors.forename: Kotoha
authors.initials: K
authors.lastname: Tane
authors.forename: Nana
authors.initials: N
authors.lastname: Toyoda
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002417:Cattle; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000254:growth & development; D018920:Coculture Techniques / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
chemical_list: D019485:Bone Morphogenetic Proteins