%0 Journal Article
%T Neuronal migration defects in the Loa dynein mutant mouse
%A Kassandra M Ori-McKenney
%A Richard B Vallee
%J Neural Development
%D 2011
%I BioMed Central
%R 10.1186/1749-8104-6-26
%X 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.Cytoplasmic dynein is a minus-end directed microtubule motor protein involved in a wide variety of functions. In order to perform such diverse activities in the cell, dynein makes use of numerous regulatory partners, including dynactin, LIS1, NudE and NudEL [1-3]. LIS1 and NudE/L, in particular, have received considerable attention for their role in brain development [4-7]. Sporadic mutations in LIS1 cause type I, or classical, lissencephaly, a severe brain developmental disease characterized by a smooth cortical surface [8]. Patients with lissencephaly exhibit lamination defects of the cerebral cortex, consistent with a defect in neuronal migration. Developmental analysis of LIS1 mutant mouse lines has shown that a reduction of LIS1 protein leads to neocortical organization defects in a dose-dependent manner [5,9-11]. Live analysis of embryonic rat brain subjected to LIS1 RNA interference (RNAi) has directly demonstrated defects in neural progenitor cell division, radial migration, and axon elongation [7,12]. The genes encoding NudE and NudEL, Nde1 and Ndel1, are closely related and interact genetically with LIS1 and cytoplasmic dynein [13]. Nde1 and Ndel1 mutant mice exhibit either microcephalic or lissencephalic brain phenotypes, consistent with a functional relationship to LIS1 [6,14-16].Several studies have focused on the role of genes in the dynein pathway in mammalian brain development. However, there are no genetic models with
%U http://www.neuraldevelopment.com/content/6/1/26