The molecular analysis of the development of cerebellum by using zebrafish mutants

为了了解控制小脑神经元发育的基因，我们研究了斑马鱼突变体gazami（gaz）和shiomaneki（sio）。通过定位克隆，我们将gaz突变定位到编码核蛋白颅面发育蛋白1（cfdp 1）的基因上。在前神经外胚层，凋亡细胞的数量在突变体幼虫增加。我们还发现，增殖细胞增加突变体在4 dpf。我们的研究结果表明Cfdp 1在神经前体细胞的分化和/或神经前体细胞的增殖中起作用，sio突变体表现为颗粒细胞轴突的错误定位。sio突变定位于编码基底膜成分Ⅳ型胶原α 6的基因，sio幼虫表现出基底膜结构的破坏。这些结果提示，神经元与基底膜的相互作用对小脑颗粒细胞的轴突发生具有重要意义。

To understand the genes that control the development of cerebellar neurons, we investigated the zebrafish mutants gazami(gaz) and shiomaneki(sio).The gaz mutant larvae showed a strong reduction of granule cells. By the positional cloning, we mapped the gaz mutation to the gene encoding a nuclear protein, cranio facial development protein1(cfdp1). In the anterior neuroectoderm, the number of apoptotic cells was increased in the mutant larvae. We also found that proliferating cells were increased in mutants at 4 dpf. Our findings suggest that Cfdp1 function in the differentiation from the neural progenitors and/or proliferation of neural progenitor cells.The sio mutants displayed mistargeted axon of granule cells. The sio mutation mapped to the gene encodes type IV collagen a6 whish serve as a component of basement membrane.The sio larvae showed the disruption of basement membrane structure. These results suggest that the interaction between neuron and basement membrane is important for the axogenesis of cerebellar granule cells.