Role of LIS1 in cell division and migration of neural progenitors and its relevance to lissencephaly

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1)LIS1 expression in gial cells.We have immunohistochemically investigated LIS1 expression in glial cells. In the rat brain, cells in astrocytic lineage expressed LIS1 as well as neuronal cells. In human glioma tissues, LIS1 was expressed in various types of glioma, regardless of histological type and the degree of anaplasia. Of note, some of the glioma cells undergoing mitosis and those infiltrating the surrounding brain parenchyma showed strong LIS1 expression. Comparable expression pattern was observed in immunohistochemistry for dynein, dynactin, NudE/NudEL and NudC, suggesting that LIS1, together with its associating proteins, play a significant role in migration and division of glial cells.2)Phenotypic effects of overexpression of dominant-negative LIS1We have subcloned a C6 glioma cell line overexpressing dominant-negative LIS1 (C6-LIS1N). In C6-LIS1N cells, cell polarity was significantly lost and migration was dramatically inhibited. However, they were capable of divide, indicating that LIS1 function differently in cell migration and mitosis.3)Dominant-negative LIS1 retrovirus vectorWe have generated dominant-negative LIS1 encoding retrovirus vector and injected in vivo into the subventricular zone of the early postnatal rat. Increased number of glial progenitors showed multipolar morphology compared to those infected with control retrovirus and their migration was dramatically inhibited. However, cell division was rather activated by dominant-negative LIS1 retrovirus infection. This again indicates cell migration and division are independently regulated by LIS1.In summary, we have demonstrated that LIS1 is expressed in cells in glial lineage as well as neuronal cells. LIS1 is likely to regulate microtubule function independently in cell migration and division. These findings provides a foundation for understanding the histogenesis of lissencephalic brains.