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Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue

Nature Neuroscience volume 10, pages 970–979 (2007)Cite this article

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.

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Figure 1: Time-lapse fluorescence microscopy of triple-labeled neural precursor cells in live brain slices.
Figure 2: Inhibition of LIS1 and dynein function in migrating neural precursor cells.
Figure 3: Analysis of centrosome movement (a,b) Centrosomal movement in control cells and cells treated with drugs or subjected to RNAi.
Figure 4: Nuclear movement in cells treated with drugs, subjected to RNAi or expressing dominant-negative cDNA constructs.
Figure 5: Inhibition of myosin II expression or function in migrating neural precursor cells.
Figure 6: Microtubule orientation in migrating neural precursor cells in brain slices.
Figure 7: Localization of cytoplasmic dynein during the migratory cycle.

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Acknowledgements

We thank P. Canoll for comments and suggestions. This work was supported by grants from the US National Institutes of Health (HD40182 and GM47434 to R.B.V.) and by the March of Dimes.

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Author notes

  1. Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, New York, New York 10032, USA.

Authors and Affiliations

  1. Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University, 630 W 168th Street, New York, New York, 10032, USA

    Jin-Wu Tsai

  2. Department of Pathology and Cell Biology. Columbia University, 630 W 168th Street, New York, 10032, New York, USA

    K Helen Bremner & Richard B Vallee

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  1. Jin-Wu Tsai
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Correspondence to Richard B Vallee.

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Tsai, JW., Bremner, K. & Vallee, R. Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue. Nat Neurosci 10, 970–979 (2007). https://doi.org/10.1038/nn1934

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