Deficiency of Fhl2 leads to delayed neuronal cell migration and premature astrocyte differentiation.

The four and a half LIM domains protein 2 (Fhl2) is an adaptor protein capable of mediating protein-protein interactions. Here, we report for the first time phenotypic changes in the brain of Fhl2-deficient mice. We showed that Fhl2 is expressed in neural stem cells, precursors and mature cells of neuronal lineage. Moreover, Fhl2 deficiency leads to delayed neuroblast migration , premature astroglial differentiation of neural stem cells (NSCs) , and a gliosis-like accumulation of glial fibrillary acidic protein (GFAP)-positive astrocytes that substantially increases with age. Collectively, Fhl2-deficiency in the brain interrupts the maintenance and the balanced differentiation of adult NSCs, resulting in preferentially glial differentiation and early exhaustion of the NSC pool required for adult neurogenesis.