Article abstract
Nature Neuroscience 12, 839 - 847 (2009)
Published online: 14 June 2009 | doi:10.1038/nn.2323
Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity
Ashwin Woodhoo1, Maria B Duran Alonso1, Anna Droggiti1, Mark Turmaine1, Maurizio D'Antonio2, David B Parkinson3, Daniel K Wilton1, Raya Al-Shawi4, Paul Simons4, Jie Shen5, Francois Guillemot6, Freddy Radtke7, Dies Meijer8, M Laura Feltri2, Lawrence Wrabetz2, Rhona Mirsky1 & Kristján R Jessen1
Abstract
Notch signaling is central to vertebrate development, and analysis of Notch has provided important insights into pathogenetic mechanisms in the CNS and many other tissues. However, surprisingly little is known about the role of Notch in the development and pathology of Schwann cells and peripheral nerves. Using transgenic mice and cell cultures, we found that Notch has complex and extensive regulatory functions in Schwann cells. Notch promoted the generation of Schwann cells from Schwann cell precursors and regulated the size of the Schwann cell pool by controlling proliferation. Notch inhibited myelination, establishing that myelination is subject to negative transcriptional regulation that opposes forward drives such as Krox20. Notably, in the adult, Notch dysregulation resulted in demyelination; this finding identifies a signaling pathway that induces myelin breakdown in vivo. These findings are relevant for understanding the molecular mechanisms that control Schwann cell plasticity and underlie nerve pathology, including demyelinating neuropathies and tumorigenesis.
- Department of Cell and Developmental Biology, University College London, London, UK.
- DIBIT, San Raffaele Scientific Institute, Milan, Italy.
- Peninsula Medical School, Plymouth, UK.
- Department of Medicine, University College London, London, UK.
- Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- National Institute for Medical Research, London, UK.
- Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland.
- Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands.
Correspondence to: Kristján R Jessen1 e-mail: k.jessen@ucl.ac.uk
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