Papel de las proteínas BMPs en la regulación de la neurogénesis hipocampal adulta

Neural stem cells generate new granule neurons in the hippocampal dentate gyrus throughout the adult life in most mammalian species. These new neurons play a key role in spatial learning and pattern separation. However, the molecular mechanisms that control their dendritic arborization and morphological maturation in the adult hippocampus remain poorly understood. Local niche signals, such as the Bone Morphogenetic Protein (BMP) family of ligands, could potentially participate in this process. We hereby show that BMP2/4/6, but not BMP7, increase neuronal complexity of rat hippocampal neurons generated from adult hippocampal progenitros in vitro, affecting both primary and secondary dendritic length. We also show that downregulation of BMP receptors, BMPR2 (Type II receptor) and ACVR1 (Type I receptor), impairs the response of the neurons to BMP6 and thus reduces neuronal complexity and maturation. On the other hand, overexpression of a constitutive active form of ACVR1 using lenti and retroviruses recapitulates the maturation effect of BMP6 in vitro. Future studies employing postnatal electroporation of a construct containing the constitutive active form of ACVR1 will address if the role BMP signaling is conserved in vivo.