| Promotion of proliferation in the developing cerebral cortex by EphA4 forward signaling. | |
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MedLine Citation:
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PMID: 19542359 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Eph receptors are widely expressed during cerebral cortical development, yet a role for Eph signaling in the generation of cells during corticogenesis has not been shown. Cortical progenitor cells selectively express one receptor, EphA4, and reducing EphA4 signaling in cultured progenitors suppressed proliferation, decreasing cell number. In vivo, EphA4(-/-) cortex had a reduced area, fewer cells and less cell division compared with control cortex. To understand the effects of EphA4 signaling in corticogenesis, EphA4-mediated signaling was selectively depressed or elevated in cortical progenitors in vivo. Compared with control cells, cells with reduced EphA4 signaling were rare and mitotically inactive. Conversely, overexpression of EphA4 maintained cells in their progenitor states at the expense of subsequent maturation, enlarging the progenitor pool. These results support a role for EphA4 in the autonomous promotion of cell proliferation during corticogenesis. Although most ephrins were undetectable in cortical progenitors, ephrin B1 was highly expressed. Our analyses demonstrate that EphA4 and ephrin B1 bind to each other, thereby initiating signaling. Furthermore, overexpression of ephrin B1 stimulated cell division of neighboring cells, supporting the hypothesis that ephrin B1-initiated forward signaling of EphA4 promotes cortical cell division. |
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Authors:
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Hilary A North; Xiumei Zhao; Sharon M Kolk; Meredith A Clifford; Daniela M Ziskind; Maria J Donoghue |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Development (Cambridge, England) Volume: 136 ISSN: 0950-1991 ISO Abbreviation: Development Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-22 Completed Date: 2009-09-24 Revised Date: 2010-07-02 |
Medline Journal Info:
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Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
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Languages: eng Pagination: 2467-76 Citation Subset: IM |
Affiliation:
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Department of Biology, Georgetown University, 334 Reiss Science Building, Washington, DC 20057, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Communication Cell Proliferation Cells, Cultured Cerebral Cortex / cytology, embryology*, metabolism* Embryonic Stem Cells / cytology, metabolism Ephrin-B1 / genetics, metabolism Female Gene Expression Regulation, Developmental Ligands Mice Mice, Inbred C57BL Mice, Knockout Models, Neurological Pregnancy Receptor, EphA4 / deficiency, genetics, metabolism* Recombinant Proteins / genetics, metabolism Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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5T32DA00729/DA/NIDA NIH HHS; R01 NS 9979-02/NS/NINDS NIH HHS; T32 NS041231-09/NS/NINDS NIH HHS; T32NS041231/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Efnb1 protein, mouse; 0/Ephrin-B1; 0/Ligands; 0/Recombinant Proteins; EC 2.7.10.1/Receptor, EphA4 |
| Comments/Corrections | |
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