@article{656e99385faa42498977ae398c71f319,
title = "Reelin Controls Neuronal Positioning by Promoting Cell-Matrix Adhesion via Inside-Out Activation of Integrin α5β1",
abstract = "Birthdate-dependent neuronal layering is fundamental to neocortical functions. The extracellular protein Reelin is essential for the establishment of the eventual neuronal alignments. Although this Reelin-dependent neuronal layering is mainly established by the final neuronal migration step called {"}terminal translocation{"} beneath the marginal zone (MZ), the molecular mechanism underlying the control by Reelin of terminal translocation and layer formation is largely unknown. Here, we show that after Reelin binds to its receptors, it activates integrin α5β1 through the intracellular Dab1-Crk/CrkL-C3G-Rap1 pathway. This intracellular pathway is required for terminal translocation and the activation of Reelin signaling promotes neuronal adhesion to fibronectin through integrin α5β1. Since fibronectin is localized in the MZ, the activated integrin α5β1 then controls terminal translocation, which mediates proper neuronal alignments in the mature cortex. These data indicate that Reelin-dependent activation of neuronal adhesion to the extracellular matrix is crucial for the eventual birth-date-dependent layering of the neocortex.",
author = "Katsutoshi Sekine and Takeshi Kawauchi and Kubo, {Ken Ichiro} and Takao Honda and Joachim Herz and Mitsuharu Hattori and Tatsuo Kinashi and Kazunori Nakajima",
note = "Funding Information: This project was supported by the Strategic Research Program for Brain Sciences (“Understanding of molecular and environmental bases for brain health”), Grant-in-Aid for Scientific Research, Global COE Program of the Ministry of Education, Culture, Sports, and Science and Technology of Japan, and Keio Gijuku Academic Development Funds. J.H. is supported by grants from the NIH, AHAF, the Consortium for Frontotemporal Dementia Research, and SFB780. We thank Drs. T. Curran (reelin); J. Cooper (dab1); F. Miller (Tα1 vector); D. Turner (mU6-provector); M. Matsuda (c3g); H. Kitayama (rap1a); N. Minato (spa1); L. Huganir (n-cadherin); T. Tsuji (integrin α3); M. Ginsberg (talin1); J. Takagi (2A-reelin); C. Cepko (pCALNL vector); T. Miyata (Tα1-Cre vector); and J. Miyazaki (pCAGGS vector) for providing the plasmids, and all of the members of the Nakajima laboratory for discussion. K.S. is a research fellow of the Japan Society for the Promotion of Science. K.S. designed and performed all of the experiments, analyzed the data, and wrote the manuscript. T. Kawauchi designed the initial experiments, analyzed the data, and wrote the manuscript. K.K. supported the preparation of Reelin, performed some in utero electroporation, and analyzed the data. T.H. constructed a part of the Dab1 expression vectors and analyzed the data. J.H. and M.H. provided the mutant mice, and J.H. edited the paper. T. Kinashi designed the integrin experiments and analyzed the data. K.N. supervised the whole project, analyzed the data, and wrote the manuscript. ",
year = "2012",
month = oct,
day = "18",
doi = "10.1016/j.neuron.2012.07.020",
language = "English (US)",
volume = "76",
pages = "353--369",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",
}