Early-onset generalized torsion dystonia, also known as DYT1 dystonia, is a childhood onset heritable neurological movement disorder involving painful, involuntary muscle contractions, sustained abnormal postures, and repetitive movements. It is caused by a GAG deletion in the Tor1A gene located on chromosome 9. TorsinA, the product of the Tor1A gene, is expressed throughout the brain beginning early in embryonic development. It plays a role in the regulation of nuclear envelope-cytoskeletal interactions, and presumably nuclear translocation. Since nuclear translocation, powered by cytoskeletal traction, is critical for cell proliferation and migration, we examined whether neurogenesis and neuronal migration are affected in Tor1A–/– mouse brain. Our data show that interkinetic nuclear migration and the pattern of migration of newly generated neurons are impaired in the dorsal forebrain of the Tor1A–/– embryo. However, neurogenesis is not altered significantly. The rate of migration of cells from explants of the medial ganglionic eminence is also impaired in the Tor1A–/– embryo. Thus, loss of torsinA results in subtle but significant alterations in cell proliferation and migration in the embryonic forebrain. These subtle developmental changes are consistent with a lack of significant changes in neuronal numbers, neuronal positioning or size of brain regions in DYT1 dystonia patients.

Keywords:
Dystonia, DYT1, Medial ganglionic eminence, Nkx2-1
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