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Science 330 (6012): 1834-1838

Copyright © 2010 by the American Association for the Advancement of Science

Siah Regulation of Pard3A Controls Neuronal Cell Adhesion During Germinal Zone Exit

Jakub K. Famulski,*,{dagger} Niraj Trivedi,* Danielle Howell, Yuan Yang,{ddagger} Yiai Tong, Richard Gilbertson, David J. Solecki§

Abstract: The brain’s circuitry is established by directed migration and synaptogenesis of neurons during development. Although neurons mature and migrate in specific patterns, little is known about how neurons exit their germinal zone niche. We found that cerebellar granule neuron germinal zone exit is regulated by proteasomal degradation of Pard3A by the Seven in Absentia homolog (Siah) E3 ubiquitin ligase. Pard3A gain of function and Siah loss of function induce precocious radial migration. Time-lapse imaging using a probe to measure neuronal cell contact reveals that Pard3A promotes adhesive interactions needed for germinal zone exit by recruiting the epithelial tight junction adhesion molecule C to the neuronal cell surface. Our findings define a Siah-Pard3A signaling pathway that controls adhesion-dependent exit of neuronal progenitors or immature neurons from a germinal zone niche.

Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.

* These authors contributed equally to this work.

{dagger} Present address: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.

{ddagger} Present address: Department of Physiology, Development and Neuroscience, Anatomy Building, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

§ To whom all correspondence should be addressed. E-mail: david.solecki{at}stjude.org


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