Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Cell. 2012 Jun 22;149(7):1549-64. doi: 10.1016/j.cell.2012.04.046.
Secretory fibroblast growth factors (FGFs) and their receptors are known for their regulatory function in the early stages of neural development. FGF13, a nonsecretory protein of the FGF family, is expressed in cerebral cortical neurons during development and is a candidate gene for syndromal and nonspecific forms of X-chromosome-linked mental retardation (XLMR). However, its function during development remains unclear. We show that FGF13 acts intracellularly as a microtubule-stabilizing protein required for axon and leading process development and neuronal migration in the cerebral cortex. FGF13 is enriched in axonal growth cones and interacts directly with microtubules. Furthermore, FGF13 polymerizes tubulins and stabilizes microtubules. The loss of FGF13 impairs neuronal polarization and increases the branching of axons and leading processes. Genetic deletion of FGF13 in mice results in neuronal migration defects in both the neocortex and the hippocampus. FGF13-deficient mice also exhibit weakened learning and memory, which is correlated to XLMR patients' intellectual disability.
分泌型成纤维细胞生长因子（FGFs）及其受体在神经发育的早期阶段具有调节功能。FGF13 是 FGF 家族中的一种非分泌性蛋白，在发育过程中表达于大脑皮层神经元中，是综合征型和非特异性 X 连锁智力低下（XLMR）的候选基因。然而，其在发育过程中的功能尚不清楚。我们发现 FGF13 在细胞内作为微管稳定蛋白发挥作用，对于大脑皮层中的轴突和前导过程发育以及神经元迁移是必需的。FGF13 在轴突生长锥中富集，并与微管直接相互作用。此外，FGF13 聚合微管蛋白并稳定微管。FGF13 的缺失会损害神经元极化，并增加轴突和前导过程的分支。在小鼠中敲除 FGF13 会导致新皮层和海马体中的神经元迁移缺陷。FGF13 缺陷型小鼠还表现出学习和记忆能力减弱，这与 XLMR 患者的智力残疾相关。
