Emerging roles for TGF‐β1 in nervous system development

Abstract

Transforming growth factor betas (TGF‐βs) 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‐β1 has been widely recognized as an injury‐related cytokine, specially associated with astrocyte scar formation in response to brain injury. TGF‐βs family is represented by three isoforms: TGF‐β1, ‐β2 and ‐β3, 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‐β 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‐β. Very few data are available concerning the intracellular pathway required for the effect of TGF‐β in brain cells. Recently, emerging data on TGF‐β1 and its signaling molecules have been suggesting that besides its role in brain injury, TGF‐β1 might be a crucial regulator of CNS development. In this review, we will focus on TGF‐βs members, specially TGF‐β1, in neuron and astrocyte development. We will discuss some advances concerning the emerging scenario of TGF‐β1 and its signaling pathways as putative modulators of astrocyte biology and their implications as a novel mediator of cellular interactions in the CNS.