Abstract
During neurogenesis, multiple regulatory networks integrate extracellular and intracellular signals to ensure proper final numbers for each neuronal subtype at the end of the developmental process. The Activin/TGF-β signaling cascade is one of the main players of neurogenesis in vertebrates, balancing proliferation and differentiation of neural stem cells by regulating gene expression via the R-Smads transcription factors. Despite their equivalent upstream activation mechanism, Smad2 and Smad3 functions can be redundant or opposite depending on the particular context of the cell. We demonstrate that R-Smad simultaneously cooperate and antagonize in the regulation of gene expression in the context of vertebrate neurogenesis. We propose a model where synergism and antagonism appear as a consequence of the competition between Smad2 and Smad3 to form the different transcriptionally active heterotrimers with Smad4. This dual interplay of R-Smads significantly modulates the role of TGF-β pathway in the balance between proliferation and differentiation in the developing vertebrate spinal cord.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.