title: Activin A promotes neuronal differentiation of cerebrocortical neural progenitor cells.
abstract: BACKGROUND
  Activin A is a protein that participates principally in reproductive functions. In the adult brain, Activin is neuroprotective, but its role in brain development is still elusive.
  
  
  RESULTS
  We studied if Activin A influences proliferation, differentiation or survival in rat cerebrocortical neural progenitor cells (NPC). After stimulation of NPC with Activin A, phosphorylation and nuclear translocation of Smad 2/3 were induced. In proliferating NPC, Activin produced a significant decrease in cell area and also a discrete increase in the number of neurons in the presence of the mitogen Fibroblast Growth Factor 2. The percentages of cells incorporating BrdU, or positive for the undifferentiated NPC markers Nestin and Sox2, were unchanged after incubation with Activin. In differentiating conditions, continuous treatment with Activin A significantly increased the number of neurons without affecting astroglial differentiation or causing apoptotic death. In cells cultured by extended periods, Activin treatment produced further increases in the proportion of neurons, excluding premature cell cycle exit. In clonal assays, Activin significantly increased neuronal numbers per colony, supporting an instructive role. Activin-induced neurogenesis was dependent on activation of its receptors, since incubation with the type I receptor inhibitor SB431542 or the ligand-trap Follistatin prevented neuronal differentiation. Interestingly, SB431542 or Follistatin by themselves abolished neurogenesis and increased astrogliogenesis, to a similar extent to that induced by Bone Morphogenetic Protein (BMP)4. Co-incubation of these Activin inhibitors with the BMP antagonist Dorsomorphin restored neuronal and astrocytic differentiation to control levels.
  
  
  CONCLUSIONS
  Our results show an instructive neuronal effect of Activin A in cortical NPC in vitro, pointing out to a relevant role of this cytokine in the specification of NPC towards a neuronal phenotype.
authors.affiliation: Instituto de Fisiología Celular-Neurociencias, Universidad Nacional Autónoma de México, México, México.
authors.forename: Griselda
authors.initials: G
authors.lastname: Rodríguez-Martínez
authors.forename: Anayansi
authors.initials: A
authors.lastname: Molina-Hernández
authors.forename: Iván
authors.initials: I
authors.lastname: Velasco
mesh_terms: D029404:Activin Receptors / Q000378:metabolism; D028341:Activins / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D051785:Smad Proteins; C422405:activin A; D028341:Activins; D029404:Activin Receptors