Molecular and cellular mechanisms contributing to the regulation, proliferation and differentiation of neural stem cells in the adult dentate gyrus

Abstract

Adult neural stem cells (NSCs) are a potential endogenous source for neuronal cell replacement in the diseased adult central nervous system (CNS). However, the recruitment of adult NSCs for repair is hampered by the current lack of knowledge about the cellular and molecular mechanisms that control their behavior in vivo. We have previously demonstrated that environment-derived signals control the fate choice of adult NSCs. More recently we have provided evidence that in the adult hippocampal dentate gyrus - one of the two neurogenic regions of the adult CNS - specialized astrocytes provide signals that instruct NSCs to adopt a neuronal fate. In this review I will examine in vitro and in vivo the molecular mechanisms underlying the neuronal fate instruction of adult NSCs by the local astrocyte population in the adult hippocampus. In particular, I will focus on the Wnt family of proteins, which we have found to be expressed in adult hippocampal astrocytes; our preliminary studies have also shown that these proteins enhance the generation of neurons from adult NSCs in vitro.