Abstract
Haplo-insufficiency of human Lis1 causes lissencephaly. Reduced Lis1 activity in both humans and mice results in a neuronal migration defect. Here we show that Drosophila Lis1 is highly expressed in the nervous system. Lis1 is essential for neuroblast proliferation and axonal transport, as shown by a mosaic analysis using a Lis1 null mutation. Moreover, it is cell-autonomously required for dendritic growth, branching and maturation. Analogous mosaic analysis shows that neurons containing a mutated cytoplasmic-dynein heavy chain (Dhc64C) exhibit phenotypes similar to Lis1 mutants. These results implicate Lis1 as a regulator of the microtubule cytoskeleton and show that it is important for diverse physiological functions in the nervous system.
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Acknowledgements
We thank T. Hays and W. E. Theurkauf for reagents, L-H. Tsai for sharing results before publication, and R. Kopito and members of the Luo laboratory for discussions and comments on the manuscript. Z.L. is a fellow of the Epilepsy Training Grant from Stanford University. This work was supported by NIH grant R01-NS36623 and fellowships from the McKnight, Klingenstein and Sloan foundations to L.L.
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Liu, Z., Steward, R. & Luo, L. Drosophila Lis1 is required for neuroblast proliferation, dendritic elaboration and axonal transport. Nat Cell Biol 2, 776–783 (2000). https://doi.org/10.1038/35041011
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DOI: https://doi.org/10.1038/35041011
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