Neuron-derived FGF9 is essential for scaffold formation of Bergmann radial fibers and migration of granule neurons in the cerebellum.
Neuron-derived FGF9 is essential for scaffold formation of Bergmann radial fibers and migration of granule neurons in the cerebellum.
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DOI：
10.1016/j.ydbio.2009.02.011
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发表时间：
2009-05-01
影响因子：
2.7
通讯作者：
Wang, Fen
中科院分区：
文献类型：
--
作者：
Lin, Yongshun;Chen, Lijie;Lin, Chunhong;Luo, Yongde;Tsai, Robert Y. L.;Wang, Fen
关键词：
虽然成纤维细胞生长因子9(FGF9)在中枢神经系统(CNS)中广泛表达，但FGF9在神经发育中的作用尚不清楚。为了解决这个问题，我们在神经管中特异性地删除了Fgf9基因，并证明了FGF9在小脑颗粒神经元出生后的迁移中起着关键作用。Fgf9基因缺失的小鼠表现出严重的共济失调，伴随着Bergmann纤维支架形成的中断，颗粒神经元迁移受损，以及浦肯野细胞成熟障碍。体外培养的野生型或Fgf9缺失的胶质细胞呈星状形态。与野生型神经元共培养，但不与Fgf9缺陷型神经元共培养，或用FGF1或FGF9处理后，细胞呈放射状胶质细胞形态。原位杂交显示Fgf9表达于神经元，免疫组织化学染色显示FGF9广泛分布于神经元和Bergmann神经胶质纤维。遗传学分析表明，FGF9在小脑发育过程中的活性主要由FGF1和FGF2受体转导。此外，抑制MAPK通路，而不是PI3K/AKT通路，抑制了FGF9的活性，从而导致神经胶质细胞形态的改变，提示FGF9的活性是由MAPK途径介导的。这项工作表明，颗粒神经元分泌FGF9来控制Bergmann纤维支架的形成，而Bergmann纤维支架又引导它们自身向内迁移和浦肯野细胞的成熟。
Although fibroblast growth factor 9 (FGF9) is widely expressed in the central nervous system (CNS), the function of FGF9 in neural development remains undefined. To address this question, we deleted the Fgf9 gene specifically in the neural tube and demonstrated that FGF9 plays a key role in the postnatal migration of cerebellar granule neurons. Fgf9-null mice showed severe ataxia associated with disrupted Bergmann fiber scaffold formation, impaired granule neuron migration, and upset Purkinje cell maturation. Ex vivo cultured wildtype or Fgf9-null glia displayed a stellate morphology. Coculture with wildtype neurons, but not Fgf9-deficient neurons, or treating with FGF1 or FGF9 induced the cells to adopt a radial glial morphology. In situ hybridization showed that Fgf9 was expressed in neurons and immunostaining revealed that FGF9 was broadly distributed in both neurons and Bergmann glial radial fibers. Genetic analyses revealed that the FGF9 activities in cerebellar development are primarily transduced by FGF receptors 1 and 2. Furthermore, inhibition of the MAP kinase pathway, but not the PI3K/AKT pathway, abrogated the FGF activity to induce glial morphological changes, suggesting that the activity is mediated by the MAP kinase pathway. This work demonstrates that granule neurons secrete FGF9 to control formation of the Bergmann fiber scaffold, which in turn, guides their own inward migration and maturation of Purkinje cells.
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影响因子：
5.3
作者：
Ohkubo, Y;Uchida, AO;Vaccarino, FM
通讯作者：
Vaccarino, FM
DOI：
10.1083/jcb.100.2.384
发表时间：
1985-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hatten ME
通讯作者：
Hatten ME
影响因子：
4.2
作者：
Cinaroglu, A;Ozmen, Y;Bugra, K
通讯作者：
Bugra, K
影响因子：
4.6
作者：
Lin, Yongshun;Liu, Guoqin;Wang, Fen
通讯作者：
Wang, Fen
影响因子：
64.5
作者：
Colvin, JS;Green, RP;Ornitz, DM
通讯作者：
Ornitz, DM