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Open Access Research article

Neuronal migration defects in the Loa dynein mutant mouse

Kassandra M Ori-McKenney12 and Richard B Vallee1*

Author Affiliations

1 Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA

2 Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA

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Neural Development 2011, 6:26  doi:10.1186/1749-8104-6-26

Published: 25 May 2011



Cytoplasmic dynein and its regulatory proteins have been implicated in neuronal and non-neuronal cell migration. A genetic model for analyzing the role of cytoplasmic dynein specifically in these processes has, however, been lacking. The Loa (Legs at odd angles) mouse with a mutation in the dynein heavy chain has been the focus of an increasing number of studies for its role in neuron degeneration. Despite the location of this mutation in the tail domain of the dynein heavy chain, we previously found a striking effect on coordination between the two dynein motor domains, resulting in a defect in dynein run length in vitro and in vivo.


We have now tested for effects of the Loa mutation on neuronal migration in the developing neocortex. Loa homozygotes showed clear defects in neocortical lamination and neuronal migration resulting from a reduction in the rate of radial migration of bipolar neurons.


These results present a new genetic model for understanding the dynein pathway and its functions during neuronal migration. They also provide the first evidence for a link between dynein processivity and somal movement, which is essential for proper development of the brain.