|Budget Amount *help
¥2,600,000 (Direct Cost : ¥2,600,000)
Fiscal Year 1995 : ¥2,600,000 (Direct Cost : ¥2,600,000)
Post-transcriptional regulation of gene expression is assumed to play important roles in the development and plasticity of the nervous system by controlling the alternative splicing, stability, translation and intracellular transport of mRNA molecules. However, very little has been elucidated about gene products regulating these post-transcriptional events in the nervous system. We have been succsessful in identifying the candidates of the gene products involved in the post-transcriptional regulation in the nervous system as described in the follows :
1. Drosophila neural RNA-binding protein, Musashi.
musashi, encoding a neural RNA-binding protein, was identified in the screening of mutants showing phenotypes in the Drosophila nervous system. Based on its loss-of-function phenotype, Musashi was likely to be required for the asymmetric cell division of the precursor cells of the Drosophila adult peripheral nervous system (adult external sensory organ). It is proposed that Musashi and othe
r neural RNA-binding protein Elav, which is specifically expressed in the Drosophila post-mitotic neuron, form a new kind of gene family of neural RNA-binding proteins that are essential for the neural development by regulating the expression of the downstream genes.
2. Isolation and characterization of the mammalian homologue of the Musashi, mouse-Musashi-1.
To elucidate the role of Musashi family in the mammalian nervous system, the gene encoding the mammalian homologue of musashi, mouse-musashi-1 (m-msi-1), was isolated by low stringent hybridizations. Bacterially-expressed m-Mshi-1 protein was shown to have RNA-binding activities in vitro by the Northwesternblot analysis. m-msi-1 was shown to be preferentially expressed in the nervous system, especially in the mitotic active neural precursor cells. The low density culture of the neuroepithelial cell has shown that m-Mshi-1 is localized to the stem cell side during its asymmetric cell division. Based on these expression pattern and its analogy to the Drosophila musashi, m-Mshi-1 was proposed to be required in the asymmetric cell division during mammalian neural development. Less