EphB Signaling Directs Peripheral Nerve Regeneration through Sox2-Dependent Schwann Cell Sorting
Autor: | Sara Ribeiro, Patrick Wingfield Digby, Ralf H. Adams, Simona Parrinello, Marina Fedorova, Robin D. S. Doddrell, Alison C. Lloyd, Ilaria Napoli, David Parkinson, Masanori Nakayama |
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Jazyk: | angličtina |
Předmět: |
Receptor
EphB2 Schwann cell Biology General Biochemistry Genetics and Molecular Biology Article SOX2 Cell Movement medicine Animals Peripheral Nerves Progenitor cell Axon Progenitor Biochemistry Genetics and Molecular Biology(all) Regeneration (biology) SOXB1 Transcription Factors Fibroblasts Cadherins Axons Cell biology Extracellular Matrix Nerve Regeneration Rats medicine.anatomical_structure nervous system Peripheral nervous system Schwann Cells Stem cell Signal Transduction |
Zdroj: | Cell. (1):145-155 |
ISSN: | 0092-8674 |
DOI: | 10.1016/j.cell.2010.08.039 |
Popis: | SummaryThe peripheral nervous system has astonishing regenerative capabilities in that cut nerves are able to reconnect and re-establish their function. Schwann cells are important players in this process, during which they dedifferentiate to a progenitor/stem cell and promote axonal regrowth. Here, we report that fibroblasts also play a key role. Upon nerve cut, ephrin-B/EphB2 signaling between fibroblasts and Schwann cells results in cell sorting, followed by directional collective cell migration of Schwann cells out of the nerve stumps to guide regrowing axons across the wound. Mechanistically, we find that cell-sorting downstream of EphB2 is mediated by the stemness factor Sox2 through N-cadherin relocalization to Schwann cell-cell contacts. In vivo, loss of EphB2 signaling impaired organized migration of Schwann cells, resulting in misdirected axonal regrowth. Our results identify a link between Ephs and Sox proteins, providing a mechanism by which progenitor cells can translate environmental cues to orchestrate the formation of new tissue.PaperFlick |
Databáze: | OpenAIRE |
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