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

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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.