title: TGF-β1 promotes cerebral cortex radial glia-astrocyte differentiation in vivo.
abstract: The major neural stem cell population in the developing cerebral cortex is composed of the radial glial cells, which generate glial cells and neurons. The mechanisms that modulate the maintenance of the radial glia (RG) stem cell phenotype, or its differentiation, are not yet completely understood. We previously demonstrated that the transforming growth factor-β1 (TGF-β1) promotes RG differentiation into astrocytes in vitro (Glia 2007; 55:1023-33) through activation of multiple canonical and non-canonical signaling pathways (Dev Neurosci 2012; 34:68-81). However, it remains unknown if TGF-β1 acts in RG-astrocyte differentiation in vivo. Here, we addressed the astrogliogenesis induced by TGF-β1 by using the intraventricular in utero injection in vivo approach. We show that injection of TGF-β1 in the lateral ventricles of E14,5 mice embryos resulted in RG fibers disorganization and premature gliogenesis, evidenced by appearance of GFAP positive cells in the cortical wall. These events were followed by decreased numbers of neurons in the cortical plate (CP). Together, we also described that TGF-β1 actions are region-dependent, once RG cells from dorsal region of the cerebral cortex demonstrated to be more responsive to this cytokine compared with RG from lateral cortex either in vitro as well as in vivo. Our work demonstrated that TGF-β1 is a critical cytokine that regulates RG fate decision and differentiation into astrocytes in vitro and in vivo. We also suggest that RG cells are heterogeneous population that acts as distinct targets of TGF-β1 during cerebral cortex development.
authors.affiliation: Laboratório de Neurobiologia Celular, Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro - Centro de Ciências da Saúde Rio de Janeiro, RJ, Brazil.
authors.forename: Joice
authors.initials: J
authors.lastname: Stipursky
authors.affiliation: Laboratório de Neurobiologia Celular, Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro - Centro de Ciências da Saúde Rio de Janeiro, RJ, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Francis
authors.affiliation: Laboratório de Neurobiologia Celular, Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro - Centro de Ciências da Saúde Rio de Janeiro, RJ, Brazil.
authors.forename: Rômulo Sperduto
authors.initials: RS
authors.lastname: Dezonne
authors.affiliation: Laboratório de Neurobiologia Celular, Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro - Centro de Ciências da Saúde Rio de Janeiro, RJ, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Bérgamo de Araújo
authors.affiliation: Laboratório de Neurobiologia Celular, Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro - Centro de Ciências da Saúde Rio de Janeiro, RJ, Brazil.
authors.forename: Lays
authors.initials: L
authors.lastname: Souza
authors.affiliation: Laboratório de Neurobiologia Celular, Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro - Centro de Ciências da Saúde Rio de Janeiro, RJ, Brazil.
authors.forename: Carolina A
authors.initials: CA
authors.lastname: Moraes
authors.affiliation: Laboratório de Neurobiologia Celular, Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro - Centro de Ciências da Saúde Rio de Janeiro, RJ, Brazil.
authors.forename: Flávia Carvalho
authors.initials: FC
authors.lastname: Alcantara Gomes
keywords: TGF-β; cerebral cortex; gliogenesis; neurogenesis; radial glia