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Fibroblast growth factor 13 is a microtubule-stabilizing protein regulating neuronal polarization and migration.

Abstract

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.

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  • Publisher Full Text
  • Authors

    , , , , , , ,

    Source

    Cell 149:7 2012 Jun 22 pg 1549-64

    MeSH

    Amino Acid Sequence
    Animals
    Axons
    Cell Movement
    Cell Polarity
    Cerebral Cortex
    Disease Models, Animal
    Female
    Fibroblast Growth Factors
    Growth Cones
    Hippocampus
    Humans
    Male
    Mental Retardation, X-Linked
    Mice
    Mice, Knockout
    Microtubules
    Molecular Sequence Data
    Neurons
    Polymerization
    Tubulin

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22726441