University Institute for Diagnostic, Interventional and Pediatric Radiology, Inselspital - University Hospital Bern, University of Bern, 3010 Bern, Switzerland.
Department of Pediatrics, Division of Molecular Pediatrics, University Hospital Erlangen, 91054 Erlangen, Germany.
J Cell Sci. 2019 Mar 18;132(6):jcs228940. doi: 10.1242/jcs.228940.
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.
四个半 LIM 结构域蛋白 2（Fhl2）是一种衔接蛋白，能够介导蛋白质-蛋白质相互作用。在这里，我们首次报告了 Fhl2 缺失小鼠大脑的表型变化。我们发现 Fhl2 表达于神经干细胞、神经元谱系的前体细胞和成熟细胞中。此外，Fhl2 缺失导致神经前体细胞迁移延迟、神经干细胞（NSCs）过早向星形胶质细胞分化，以及神经胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞的神经胶质样堆积，这种堆积随着年龄的增长而显著增加。总之，大脑中 Fhl2 的缺失中断了成年 NSCs 的维持和平衡分化，导致优先发生胶质分化，并使成年神经发生所需的 NSCs 池过早耗尽。
