title: Emerging roles for TGF-beta1 in nervous system development.
abstract: Transforming growth factor betas (TGF-betas) are known as multifunctional growth factors, which participate in the regulation of key events of development, disease and tissue repair. In central nervous system (CNS), TGF-beta1 has been widely recognized as an injury-related cytokine, specially associated with astrocyte scar formation in response to brain injury. TGF-betas family is represented by three isoforms: TGF-beta1, -beta 2 and -beta 3, all produced by both glial and neuronal cells. They are involved in essential tissue functions, including cell-cycle control, regulation of early development and differentiation, neuron survival and astrocyte differentiation. TGF-beta signaling is mediated mainly by two serine threonine kinase receptors, TGFRI and TGFRII, which activate Smad 2/3 and Smad 4 transcription factors. Phosphorylation and activation of these proteins is followed by formation of Smad 2/3-4 complex, which translocates to the nucleus regulating transcriptional responses to TGF-beta. Very few data are available concerning the intracellular pathway required for the effect of TGF-beta in brain cells. Recently, emerging data on TGF-beta1 and its signaling molecules have been suggesting that besides its role in brain injury, TGF-beta1 might be a crucial regulator of CNS development. In this review, we will focus on TGF-betas members, specially TGF-beta1, in neuron and astrocyte development. We will discuss some advances concerning the emerging scenario of TGF-beta1 and its signaling pathways as putative modulators of astrocyte biology and their implications as a novel mediator of cellular interactions in the CNS.
authors.affiliation: Instituto de Ciências Biomédicas, Departamento de Anatomia, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco F, Ilha do Fundão, 21949-590 Rio de Janeiro, RJ, Brazil.
authors.forename: Flávia Carvalho Alcantara
authors.initials: FC
authors.lastname: Gomes
authors.forename: Vivian de Oliveira
authors.initials: Vde O
authors.lastname: Sousa
authors.forename: Luciana
authors.initials: L
authors.lastname: Romão
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D002490:Central Nervous System / Q000254:growth & development*; D009457:Neuroglia / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D053773:Transforming Growth Factor beta1
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1