The Protooncogene Ski Controls Schwann Cell Proliferation and Myelination
| Autor: | Clemencia Colmenares, Peter Young, Lukas Sommer, Suzana Atanasoski, Ed Stavnezer, François Castagner, Dies Meijer, Hye Youn Lee, Lucia Notterpek, Ueli Suter, Markus U. Ehrengruber |
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| Přispěvatelé: | Molecular Genetics |
| Rok vydání: | 2004 |
| Předmět: |
animal structures
Neuroscience(all) Schwann cell Mice Transgenic Biology Transfection Schwann cell proliferation 03 medical and health sciences Myelin Mice 0302 clinical medicine Downregulation and upregulation Proto-Oncogene Proteins Proto-Oncogenes medicine Animals Remyelination Rats Wistar Transcription factor Cells Cultured Myelin Sheath 030304 developmental biology Mice Knockout 0303 health sciences General Neuroscience Regeneration (biology) Cell Cycle Cell cycle musculoskeletal system Sciatic Nerve Mice Mutant Strains Cell biology Rats DNA-Binding Proteins Mice Inbred C57BL medicine.anatomical_structure nervous system Gene Expression Regulation Schwann Cells human activities Neuroscience 030217 neurology & neurosurgery Cell Division |
| Zdroj: | Neuron, 43, 499-511. Cell Press Neuron |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2004.08.001 |
| Popis: | Schwann cell proliferation and subsequent differentiation to nonmyelinating and myelinating cells are closely linked processes. Elucidating the molecular mechanisms that control these events is key to the understanding of nerve development, regeneration, nerve-sheath tumors, and neuropathies. We define the protooncogene Ski, an inhibitor of TGF-β signaling, as an essential component of the machinery that controls Schwann cell proliferation and myelination. Functional Ski overexpression inhibits TGF-β-mediated proliferation and prevents growth-arrested Schwann cells from reentering the cell cycle. Consistent with these findings, myelinating Schwann cells upregulate Ski during development and remyelination after injury. Myelination is blocked in myelin-competent cultures derived from Ski-deficient animals, and genes encoding myelin components are downregulated in Ski-deficient nerves. Conversely, overexpression of Ski in Schwann cells causes an upregulation of myelin-related genes. The myelination-regulating transcription factor Oct6 is involved in a complex modulatory relationship with Ski. We conclude that Ski is a crucial signal in Schwann cell development and myelination. |
| Databáze: | OpenAIRE |
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