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Publication : Left-right locomotor circuitry depends on RhoA-driven organization of the neuroepithelium in the developing spinal cord.

First Author  Katayama K Year  2012
Journal  J Neurosci Volume  32
Issue  30 Pages  10396-407
PubMed ID  22836272 Mgi Jnum  J:186538
Mgi Id  MGI:5432615 Doi  10.1523/JNEUROSCI.6474-11.2012
Citation  Katayama K, et al. (2012) Left-Right Locomotor Circuitry Depends on RhoA-Driven Organization of the Neuroepithelium in the Developing Spinal Cord. J Neurosci 32(30):10396-407
abstractText  RhoA is a key regulator of cytoskeletal dynamics with a variety of effects on cellular processes. Loss of RhoA in neural progenitor cells disrupts adherens junctions and causes disorganization of the neuroepithelium in the developing nervous system. However, it remains essentially unknown how the loss of RhoA physiologically affects neural circuit formation. Here we show that proper neuroepithelial organization maintained by RhoA GTPase in both the ventral and dorsal spinal cord is critical for left-right locomotor behavior. We examined the roles of RhoA in the ventral and dorsal spinal cord by deleting the gene in neural progenitors using Olig2-Cre and Wnt1-Cre mice, respectively. RhoA-deleted neural progenitors in both mutants exhibit defects in the formation of apical adherens junctions and disorganization of the neuroepithelium. Consequently, the ventricular zone and lumen of the dysplastic region are lost, causing the left and right sides of the gray matter to be directly connected. Furthermore, the dysplastic region lacks ephrinB3 expression at the midline that is required for preventing EphA4-expressing corticospinal neurons and spinal interneurons from crossing the midline. As a result, aberrant neuronal projections are observed in that region. Finally, both RhoA mutants develop a rabbit-like hopping gait. These results demonstrate that RhoA functions to maintain neuroepithelial structures in the developing spinal cord and that proper organization of the neuroepithelium is required for appropriate left-right motor behavior.
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