Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning and climbing fiber territory on Purkinje cells
Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning and climbing fiber territory on Purkinje cells
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DOI：
10.1111/j.1460-9568.2008.06069.x
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发表时间：
2008-02-01
影响因子：
3.4
通讯作者：
Mishina, Masayoshi
中科院分区：
文献类型：
--
作者：
Watanabe, Fumihiro;Miyazaki, Taisuke;Mishina, Masayoshi
粘着斑激酶（Focal adhesion kinase，FAK）是一种非受体酪氨酸激酶，广泛表达于脑内，在细胞内外刺激的多种细胞过程中起重要作用。在这里，我们探讨了FAK在小脑发育中的作用。在小鼠小脑，FAK被发现作为微小的细胞质聚集体分布在各种神经元和胶质细胞的元素，包括浦肯野细胞（PC），Bergmann胶质细胞（BG），平行纤维（PF）-终末和攀爬纤维（CF）-终末。FAK的神经元/胶质细胞特异性消融损害了小脑的叶状结构，例如叶状结构尺寸的可变减少以及缺乏脚间和中央前裂。一些BG细胞异位位于分子层中。此外，FAK消融改变了PC上CFs和PFs的神经支配区域。CF神经支配回归到近端树突和胞体的基部，而异位棘从近端树突突出，PF通过支配异位棘来扩大其领土。此外，剩余的CFs支配PC胞体的持久性造成了多重神经支配。当选择性消融FAK在PC，减少树突状神经支配和持续的躯体神经支配的CF观察，而小脑叶和BG的细胞定位正常保留。这些结果表明，FAK在各种神经元和神经胶质细胞的元素是必需的正常的组织结构和细胞结构的形成在小脑，并为建设适当的神经支配领土和突触布线在PC。
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is widely expressed in the brain, and plays key roles in various cellular processes in response to both extracellular and intracellular stimuli. Here, we explored the role of FAK in cerebellar development. In the mouse cerebellum, FAK was found to be distributed as tiny cytoplasmic aggregates in various neuronal and glial elements, including Purkinje cells (PCs), Bergmann glia (BG), parallel fiber (PF)-terminals and climbing fiber (CF)-terminals. The neuron/glia-specific ablation of FAK impaired cerebellar foliation, such as variable decreases in foliation sizes and the lack of intercrural and precentral fissures. Some of the BG cells became situated ectopically in the molecular layer. Furthermore, the FAK ablation altered the innervation territories of CFs and PFs on PCs. CF innervation regressed to the basal portion of proximal dendrites and somata, whereas ectopic spines protruded from proximal dendrites and PFs expanded their territory by innervating the ectopic spines. Furthermore, the persistence of surplus CFs innervating PC somata caused multiple innervation. When FAK was selectively ablated in PCs, diminished dendritic innervation and persistent somatic innervation by CFs were observed, whereas cerebellar foliation and cell positioning of BG were normally retained. These results suggest that FAK in various neuronal and glial elements is required for the formation of normal histoarchitecture and cytoarchitecture in the cerebellum, and for the construction of proper innervation territory and synaptic wiring in PCs.