Article abstract
Nature Neuroscience 10, 970 - 979 (2007)
Published online: 8 July 2007 | doi:10.1038/nn1934
Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue
Jin-Wu Tsai1, K Helen Bremner2 & Richard B Vallee2
Abstract
During brain development, neural precursor cells migrate along radial glial fibers to populate the neocortex. RNA interference (RNAi) of the lissencephaly gene LIS1 (also known as PAFAH1b1) inhibits somal movement but not process extension of neural precursors in live brain slices. Here we report imaging of the subcellular events accompanying neural precursor migration and the effects of LIS1, cytoplasmic dynein and myosin II inhibition. Centrosomes move continuously and often far in advance of nuclei, which show extreme saltatory behavior. LIS1 and dynein RNAi inhibit centrosomal and nuclear movement independently, whereas myosin II inhibition blocks only nuclear translocation. Imaging of the microtubule end-binding protein 3 (EB3) reveals a centrosome-centered array of microtubules in live neural precursors under all conditions examined. Dynein is concentrated both at a swelling in the leading process reported to initiate each migratory cycle and in the soma. Thus, dynein pulls on the microtubule network from the swelling. The nucleus is transported along the trailing microtubules by dynein assisted by myosin II.
- Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University, 630 W 168th Street, New York, New York 10032, USA.
- Department of Pathology and Cell Biology. Columbia University, 630 W 168th Street, New York, New York 10032, USA.
- Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, New York, New York 10032, USA.
Correspondence to: Richard B Vallee2 e-mail: rv2025@columbia.edu
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