title: Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity.
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.
authors.affiliation: Department of Cell and Developmental Biology, University College London, UK.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Woodhoo
authors.forename: Maria B Duran
authors.initials: MB
authors.lastname: Alonso
authors.forename: Anna
authors.initials: A
authors.lastname: Droggiti
authors.forename: Mark
authors.initials: M
authors.lastname: Turmaine
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Antonio
authors.forename: David B
authors.initials: DB
authors.lastname: Parkinson
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Wilton
authors.forename: Raya
authors.initials: R
authors.lastname: Al-Shawi
authors.forename: Paul
authors.initials: P
authors.lastname: Simons
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Francois
authors.initials: F
authors.lastname: Guillemot
authors.forename: Freddy
authors.initials: F
authors.lastname: Radtke
authors.forename: Dies
authors.initials: D
authors.lastname: Meijer
authors.forename: M Laura
authors.initials: ML
authors.lastname: Feltri
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wrabetz
authors.forename: Rhona
authors.initials: R
authors.lastname: Mirsky
authors.forename: Kristján R
authors.initials: KR
authors.lastname: Jessen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003711:Demyelinating Diseases / Q000378:metabolism; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000502:physiology; D020890:Neuregulin-1 / Q000378:metabolism; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000196:embryology / Q000254:growth & development; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D051767:Early Growth Response Protein 2; D006023:Glycoproteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D051880:Receptors, Notch; C490581:Nrg1 protein, mouse; C490580:Nrg1 protein, rat; C497571:Rbpj protein, mouse; C524056:Erbb2 protein, mouse; C483804:Erbb2 protein, rat