Sci. Signal., 12 August 2008
Medicine Axonal Pathfinding in Sight
Paula A. Kiberstis
Science, AAAS, Washington, DC 20005, USA
About 1 in 1000 people are afflicted with Duanes retraction syndrome (DRS), a complex congenital eye disorder characterized by a restricted ability to move the eye(s) outward or inward. The condition is thought to arise from faulty innervation of extraocular muscles by cranial motor neurons, which probably occurs early in embryogenesis. Miyake et al. now provide genetic evidence that strongly supports this hypothesis. Studying families with a variant form of DRS, the authors discovered that the mutations responsible for the disorder fall within a gene on chromosome 2 encoding 2-chimaerin, a RacGAP signaling protein previously implicated in axonal pathfinding of corticospinal nerves in mice. The human mutations cause 2-chimaerin to become overactive, and expression of the mutant protein in a chick embryo model did indeed disrupt oculomotor axon development.
N. Miyake, J. Chilton, M. Psatha, L. Cheng, C. Andrews, W.-M. Chan, K. Law, M. Crosier, S. Lindsay, M. Cheung, J. Allen, N. J. Gutowski, S. Ellard, E. Young, A. Iannaccone, B. Appukuttan, J. T. Stout, S. Christiansen, M. L. Ciccarelli, A. Baldi, M. Campioni, J. C. Zenteno, D. Davenport, L. E. Mariani, M. Sahin, S. Guthrie, E. C. Engle, Human CHN1 mutations hyperactivate 2-chimaerin and cause Duane's retraction syndrome. Science 321, 839-843 (2008). [Abstract] [Full Text]
Citation: P. A. Kiberstis, Axonal Pathfinding in Sight. Sci. Signal. 1, ec291 (2008).
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