| Migration of sympathetic preganglionic neurons in the spinal cord is regulated by Reelin-dependent Dab1 tyrosine phosphorylation and CrkL. | |
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MedLine Citation:
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PMID: 17394141 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The actions of Reelin in neuronal positioning in the developing cortex and cerebellum are relayed by Src-family kinase (SFK)-mediated phosphorylation of Dab1. Biochemical studies show that after phosphorylation Dab1 binds to an adaptor protein, CrkL. Whether CrkL is important for Reelin signaling in vivo is unknown, because crkl(-/-) embryos die before cortical development is complete. In the developing spinal cord, Reelin and components of its signaling pathway, VLDLR, ApoER2, and Dab1, control the positioning of sympathetic preganglionic neurons (SPN); however, it is not known whether SFKs or Dab1 tyrosine phosphorylation is required. In the present study, we asked whether Reelin-controlled SPN migration depends on tyrosine phosphorylation of Dab1 by SFKs and whether CrkL is involved in SPN migration. To answer these questions, we examined the location of SPN in various mutant mouse embryos. Results showed that, in dab1(5F/5F) embryos, which express a nonphosphorylated mutant of Dab1, and in src(-/-)fyn(-/-) double knockout embryos, the location of SPN is identical to that of reeler. These results show that tyrosine phosphorylation of Dab1 by SFKs is required for Reelin-regulated SPN positioning. In addition, we found that SPN migration in crkl(-/-) showed a partial reeler phenotype, suggesting a partial loss of response of SPN to Reelin signaling. These results suggest a role for CrkL in the Reelin signaling pathway to control neuronal migration. |
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Authors:
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Yee Ping Yip; Priscilla Kronstadt-O'Brien; Christine Capriotti; Jonathan A Cooper; Joseph W Yip |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The Journal of comparative neurology Volume: 502 ISSN: 0021-9967 ISO Abbreviation: J. Comp. Neurol. Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-04-19 Completed Date: 2007-06-21 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0406041 Medline TA: J Comp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 635-43 Citation Subset: IM |
Copyright Information:
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(c) 2007 Wiley-Liss, Inc. |
Affiliation:
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Department of Neurobiology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15261, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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metabolism* Animals Cell Adhesion Molecules, Neuronal / metabolism* Cell Movement / physiology* Extracellular Matrix Proteins / metabolism* Female Gene Expression Regulation, Developmental / physiology Male Mice Mice, Inbred C57BL Mice, Knockout Nerve Tissue Proteins / genetics, metabolism* Neurons / metabolism Nuclear Proteins / metabolism* Phosphorylation Proto-Oncogene Proteins c-fyn / genetics Serine Endopeptidases / metabolism* Signal Transduction / physiology Spinal Cord / embryology*, metabolism Sympathetic Nervous System / embryology*, metabolism Tyrosine / metabolism src-Family Kinases / genetics |
| Grant Support | |
ID/Acronym/Agency:
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CA41072/CA/NCI NIH HHS; MH62180/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/CRKL protein; 0/Cell Adhesion Molecules, Neuronal; 0/Dab1 protein, mouse; 0/Extracellular Matrix Proteins; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 55520-40-6/Tyrosine; EC 2.7.1.112/Fyn protein, mouse; EC 2.7.10.2/Proto-Oncogene Proteins c-fyn; EC 2.7.10.2/src-Family Kinases; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/reelin protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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