β1-Integrin Restricts Astrocytic Differentiation of Adult Hippocampal Neural Stem Cells

Integrins are transmembrane receptors that mediate cell-extracellular matrix and cell-cell interactions. The beta 1-integrin subunit is highly expressed by embryonic neural stem cells (NSCs) and is critical for NSC maintenance in the developing nervous system, but its role in the adult hippocampal niche remains unexplored. We show that beta 1-integrin expression in the adult mouse dentate gyrus (DG) is localized to radial NSCs and early progenitors, but is lost in more mature progeny. Although NSCs in the hippocampal subgranular zone (SGZ) normally only infrequently differentiate into astrocytes, deletion of beta 1-integrin significantly enhanced astrocyte differentiation. Ablation of beta 1-integrin also led to reduced neurogenesis as well as depletion of the radial NSC population. Activation of integrin-linked kinase (ILK) in cultured adult NSCs from beta 1-integrin knockout mice reduced astrocyte differentiation, suggesting that at least some of the inhibitory effects of beta 1-integrin on astrocytic differentiation are mediated through ILK. In addition, beta 1-integrin conditional knockout also resulted in extensive cellular disorganization of the SGZ as well as non-neurogenic regions of the DG. The effects of beta 1-integrin ablation on DG structure and astrogliogenesis show sex-specific differences, with the effects following a substantially slower time-course in males. beta 1-integrin thus plays a dual role in maintaining the adult hippocampal NSC population by supporting the structural integrity of the NSC niche and by inhibiting astrocytic lineage commitment.