Activin and TGF-ß effects on brain development and neural stem cells.

Transforming Growth Factor-ß (TGF-ß) family members are ubiquitously expressed, participating in the regulation of many processes in different cell types both in embryonic and adult stages. Several members of this family, including Activins, TGF-ß1-3 and Nodal, have been implicated in the development and maintenance of various organs, in which stem cells play important roles. Although TGF-ß was initially considered an injury-related cytokine, it became clear that not only TGF-ß, but other members of this family, play critical roles in morphogenesis and cell lineage specification. During brain development, Activin and TGF-ßs as well as their cognate receptors, are expressed in different patterns. The roles of Activin and TGF-ß during CNS development are sometimes contradictory, because these proteins present different actions depending on the cell type and the context. The aim of this review is to summarize current information on the actions of TGF-ß members during developing brain, and also on Neural Stem/Progenitor Cells (NSPC). We focus on the TGF-ß subgroup, specifically on the effects of TGF-ß1 and Activin A. In the first section we describe the main characteristics of the ligands, its receptors as well as the proteins and mechanisms involved in signaling. Next, we discuss the main advances concerning TGF-ß1 and Activin actions during brain development and their roles in NSPC fate decision and neuroprotection both in vitro and in vivo. The emerging picture from these studies suggests that these growth factors can be used to manipulate neurogenesis and might help to achieve restoration after brain deterioration.