Fibroblast growth factor 13 is a microtubule-stabilizing protein regulating neuronal polarization and migration.
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.
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Qing-Feng
QF
Wu
Liu
L
Yang
Shuai
S
Li
Qiong
Q
Wang
Xiao-Bin
XB
Yuan
Xiang
X
Gao
Lan
L
Bao
Xu
X
Zhang
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism; D002465:Cell Movement; D016764:Cell Polarity; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D058105:Polymerization; D014404:Tubulin / Q000378:metabolism
D014404:Tubulin; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors