期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：18
页码：7595-7600
DOI：10.1073/pnas.0811343106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cortical GABAergic interneurons, most of which originate in the ganglionic eminences, take distinct tangential migratory trajectories into the developing cerebral cortex. However, the ligand-receptor systems that modulate the tangential migration of distinct groups of interneurons into the emerging cerebral wall remain unclear. Here, we show that netrin-1, a diffusible guidance cue expressed along the migratory routes traversed by GABAergic interneurons, interacts with {alpha}3{beta}1 integrin to promote interneuronal migration. In vivo analysis of interneuron-specific {alpha}3{beta}1 integrin, netrin-1-deficient mice ({alpha}3lox/-Dlx5/6-CIE, netrin-1-/-) reveals specific deficits in the patterns of interneuronal migration along the top of the developing cortical plate, resulting in aberrant interneuronal positioning throughout the cerebral cortex and hippocampus of conditional {alpha}3lox/-Dlx5/6-CIE, netrin-1-/- mice. These results indicate that specific guidance mechanisms, such as netrin-1-{alpha}3{beta}1 integrin interactions, modulate distinct routes of interneuronal migration and the consequent positioning of groups of cortical interneurons in the developing cerebral cortex.
