Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling
Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling
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DOI：
10.1016/s0092-8674(00)80689-3
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发表时间：
2000-03-03
期刊：
影响因子：
64.5
通讯作者：
Salinas, PC
中科院分区：
文献类型：
--
作者：
Hall, AC;Lucas, FR;Salinas, PC
突触的形成需要细胞形态的改变以及突触蛋白的上调和定位。在小脑中，苔藓纤维在与多个颗粒细胞接触并形成复杂的、多突触的肾小球莲座时经历广泛的重塑。在这里，我们发现颗粒细胞分泌因子诱导苔藓纤维轴突和生长锥重塑。这种作用被WNT拮抗剂sFRP-1阻断，并被颗粒细胞表达的WNT-7a模拟。WNT-7a还在苔藓纤维重塑区域诱导突触蛋白1聚集，这是突触发生的初步步骤。Wnt-7a突变小鼠在肾小球莲座的形态成熟和突触素i的积累方面表现出延迟。我们提出Wnt-7a可以作为突触发生因子发挥作用。
Synapse formation requires changes in cell morphology and the upregulation and localization of synaptic proteins. In the cerebellum, mossy fibers undergo extensive remodeling as they contact several granule cells and form complex, multisynaptic glomerular rosettes. Here we show that granule cells secrete factors that induce axon and growth cone remodeling in mossy fibers. This effect is blocked by the WNT antagonist, sFRP-1, and mimicked by WNT-7a, which is expressed by granule cells. WNT-7a also induces synapsin I clustering at remodeled areas of mossy fibers, a: preliminary step in synaptogenesis. Wnt-7a mutant mice show a delay in the morphological maturation of glomerular rosettes and in the accumulation of synapsin I. We propose that WNT-7a can function as a synaptogenic factor.