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Morphogenesis requires the proper migration and positioning of different cell types in the embryo. Much more is known about how cells start and guide their migrations than about how they stop when they reach their destinations. Here we provide evidence that Rbx2, a subunit of the Cullin 5-RING E3 ubiquitin ligase (CRL5) complex, stops neocortical projection neurons at their target layers. Rbx2 mutation causes neocortical and cerebellar ectopias dependent on Dab1, a key signaling protein in the Reelin pathway. SOCS7, a CRL5 substrate adaptor protein, is also required for neocortical layering. SOCS7-CRL5 complexes stimulate the ubiquitylation and turnover of Dab1. SOCS7 is upregulated during projection neuron migration, and unscheduled SOCS7 expression stops migration prematurely. Cerebellar development requires Rbx2 but not SOCS7, pointing to the importance of other CRL5 adaptors. Our results suggest that CRL5 adaptor expression is spatiotemporally regulated to modulate Reelin signaling and ensure normal neuron positioning in the developing brain.
Pubmed ID: 24210661 RIS Download
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Database of the international consortium working together to mutate all protein-coding genes in the mouse using a combination of gene trapping and gene targeting in C57BL/6 mouse embryonic stem (ES) cells. Detailed information on targeted genes is available. The IKMC includes the following programs: * Knockout Mouse Project (KOMP) (USA) ** CSD, a collaborative team at the Children''''s Hospital Oakland Research Institute (CHORI), the Wellcome Trust Sanger Institute and the University of California at Davis School of Veterinary Medicine , led by Pieter deJong, Ph.D., CHORI, along with K. C. Kent Lloyd, D.V.M., Ph.D., UC Davis; and Allan Bradley, Ph.D. FRS, and William Skarnes, Ph.D., at the Wellcome Trust Sanger Institute. ** Regeneron, a team at the VelociGene division of Regeneron Pharmaceuticals, Inc., led by David Valenzuela, Ph.D. and George D. Yancopoulos, M.D., Ph.D. * European Conditional Mouse Mutagenesis Program (EUCOMM) (Europe) * North American Conditional Mouse Mutagenesis Project (NorCOMM) (Canada) * Texas A&M Institute for Genomic Medicine (TIGM) (USA) Products (vectors, mice, ES cell lines) may be ordered from the above programs.
View all literature mentionsCenter that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.
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