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

Fhl2 (Four and a half LIM domain protein 2) 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: (i) Fhl2 is expressed in neural stem cells, precursors, and mature cells of the neuronal lineage; (ii) Fhl2 deficiency leads to delayed neuroblast migration in vivo , to (iii) premature astroglial differentiation of neural stem cells (NSC) in vitro , and to (iv) a gliosis-like accumulation of GFAP+ astrocytes in vivo that substantially increases with age. Collectively, Fhl2-deficiency in the brain interrupts the maintenance and the balanced differentiation of adult NSC, resulting in preferentially glial differentiation and early exhaustion of the NSC pool required for adult neurogenesis.