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Vol. 15, Issue 6, 2568-2579, June 2004

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A Point Mutation in the Motor Domain of Nonmuscle Myosin II-B Impairs Migration of Distinct Groups of Neurons

Xuefei Ma ^*, Sachiyo Kawamoto ^*, Yoshinobu Hara , and Robert S. Adelstein ^* 

^* Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; Neurodevelopment Institute, Sagamihara, Japan 229-1106

Submitted November 24, 2003; Revised February 23, 2004; Accepted March 2, 2004
Monitoring Editor: Thomas Pollard

We generated mice harboring a single amino acid mutation in the motor domain of nonmuscle myosin heavy chain II-B (NMHC II-B). Homozygous mutant mice had an abnormal gait and difficulties in maintaining balance. Consistent with their motor defects, the mutant mice displayed an abnormal pattern of cerebellar foliation. Analysis of the brains of homozygous mutant mice showed significant defects in neuronal migration involving granule cells in the cerebellum, the facial neurons, and the anterior extramural precerebellar migratory stream, including the pontine neurons. A high level of NMHC II-B expression in these neurons suggests an important role for this particular isoform during neuronal migration in the developing brain. Increased phosphorylation of the myosin II regulatory light chain in migrating, compared with stationary pontine neurons, supports an active role for myosin II in regulating their migration. These studies demonstrate that NMHC II-B is particularly important for normal migration of distinct groups of neurons during mouse brain development.

Abbreviations used: AES, anterior extramural precerebellar migratory stream; DCC, Deleted in Colorectal Cancer; E, embryonic day; EGL, external germinal layer; ES cell, embryonic stem cell; H&E, hematoxylin and eosin; IGL, internal granular layer; ML, molecular layer; NMHC II-B, nonmuscle myosin heavy chain II-B; P, postnatal day; RMLC-P, phosphorylated 20-kDa regulatory myosin light chain.

Corresponding author. E-mail address: adelster{at}nhlbi.nih.gov.

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