Hall A C, Lucas F R, Salinas P C
Developmental Biology Research Centre, The Randall Institute, King's College London, United Kingdom.
Cell. 2000 Mar 3;100(5):525-35. doi: 10.1016/s0092-8674(00)80689-3.
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.
突触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，苔藓纤维在与多个颗粒细胞接触并形成复杂的多突触肾小球状玫瑰花结时会经历广泛的重塑。在这里，我们表明颗粒细胞分泌诱导苔藓纤维轴突和生长锥重塑的因子。这种效应被WNT拮抗剂sFRP-1阻断，并被颗粒细胞表达的WNT-7a模拟。WNT-7a还诱导突触素I在苔藓纤维重塑区域聚集，这是突触形成的初步步骤。Wnt-7a突变小鼠在肾小球状玫瑰花结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可以作为一种突触形成因子发挥作用。
