Emerging roles for TGF-beta1 in nervous system development.
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.
Gomes
Flávia Carvalho Alcantara
FC
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.
Sousa
Vivian de Oliveira
Vde O
Romão
Luciana
L
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
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1