title: Sox10 is required for Schwann cell identity and progression beyond the immature Schwann cell stage.
abstract: Mutations in the transcription factor SOX10 cause neurocristopathies, including Waardenburg-Hirschsprung syndrome and peripheral neuropathies in humans. This is partly attributed to a requirement for Sox10 in early neural crest for survival, maintenance of pluripotency, and specification to several cell lineages, including peripheral glia. As a consequence, peripheral glia are absent in Sox10-deficient mice. Intriguingly, Sox10 continues to be expressed in these cells after specification. To analyze glial functions after specification, we specifically deleted Sox10 in immature Schwann cells by conditional mutagenesis. Mutant mice died from peripheral neuropathy before the seventh postnatal week. Nerve alterations included a thinned perineurial sheath, increased lipid and collagen deposition, and a dramatically altered cellular composition. Nerve conduction was also grossly aberrant, and neither myelinating nor nonmyelinating Schwann cells formed. Instead, axons of different sizes remained unsorted in large bundles. Schwann cells failed to develop beyond the immature stage and were unable to maintain identity. Thus, our study identifies a novel cause for peripheral neuropathies in patients with SOX10 mutations.
authors.affiliation: Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Finzsch
authors.forename: Silke
authors.initials: S
authors.lastname: Schreiner
authors.forename: Tatjana
authors.initials: T
authors.lastname: Kichko
authors.forename: Peter
authors.initials: P
authors.lastname: Reeh
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bösl
authors.forename: Dies
authors.initials: D
authors.lastname: Meijer
authors.forename: Michael
authors.initials: M
authors.lastname: Wegner
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004622:Embryo, Mammalian / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010523:Peripheral Nervous System Diseases / Q000235:genetics; D051381:Rats; D055757:SOXE Transcription Factors / Q000235:genetics*; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D055757:SOXE Transcription Factors
references.citation: Nat Genet. 1998 Jan;18(1):60-4
references.pmid: 9425902
references.citation: J Immunol. 1996 Feb 15;156(4):1515-24
references.pmid: 8568255
references.citation: Neurochem Res. 2007 Jul;32(7):1129-41
references.pmid: 17404841
references.citation: J Neurosci Methods. 1990 Feb;31(2):109-18
references.pmid: 2319811
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5161-5
references.pmid: 9560246
references.citation: J Neurosci. 1998 Jan 1;18(1):237-50
references.pmid: 9412504
references.citation: J Cell Biol. 2002 Jan 7;156(1):199-209
references.pmid: 11777940
references.citation: Nucleic Acids Res. 1999 Mar 15;27(6):1409-20
references.pmid: 10037800
references.citation: Development. 2004 Nov;131(22):5599-612
references.pmid: 15496445
references.citation: Nat Genet. 1998 Feb;18(2):171-3
references.pmid: 9462749
references.citation: J Neurochem. 2010 Feb;112(3):744-54
references.pmid: 19922439
references.citation: Nat Genet. 2000 Jun;25(2):139-40
references.pmid: 10835623
references.citation: Mol Cell Biol. 2005 Mar;25(5):1821-9
references.pmid: 15713637
references.citation: Genes Dev. 2003 Jun 1;17(11):1380-91
references.pmid: 12782656
references.citation: Mol Cell Biol. 2007 May;27(9):3521-9
references.pmid: 17325040
references.citation: EMBO Rep. 2006 Jan;7(1):52-8
references.pmid: 16311519
references.citation: Genes Dev. 2002 Jan 15;16(2):165-70
references.pmid: 11799060
references.citation: Nat Genet. 2004 Apr;36(4):361-9
references.pmid: 15004559
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2596-601
references.pmid: 15695336
references.citation: J Cell Biol. 2007 Jun 18;177(6):1051-61
references.pmid: 17576798
references.citation: Mol Cell Biol. 2000 May;20(9):3198-209
references.pmid: 10757804
references.citation: Genes Dev. 2001 Jan 1;15(1):66-78
references.pmid: 11156606
references.citation: Am J Hum Genet. 2007 Dec;81(6):1169-85
references.pmid: 17999358
references.citation: Genesis. 2004 Nov;40(3):171-5
references.pmid: 15493017
references.citation: Nat Rev Neurosci. 2005 Sep;6(9):671-82
references.pmid: 16136171
references.citation: Science. 2009 Jan 30;323(5914):651-4
references.pmid: 19179536
references.citation: Nature. 1994 Oct 27;371(6500):796-9
references.pmid: 7935840
references.citation: J Anat. 1997 Oct;191 ( Pt 3):321-36
references.pmid: 9418989
references.citation: Development. 2001 Oct;128(20):3949-61
references.pmid: 11641219
references.citation: Glia. 2008 Nov 1;56(14):1566-77
references.pmid: 18803324
references.citation: BMC Dev Biol. 2001;1:4
references.pmid: 11299042
references.citation: Neurobiol Dis. 2009 Mar;33(3):448-58
references.pmid: 19111616
references.citation: Science. 1996 Jul 26;273(5274):507-10
references.pmid: 8662541
references.citation: J Cell Biol. 2007 Jun 18;177(6):1063-75
references.pmid: 17576799
references.citation: Dev Biol. 2010 May 1;341(1):267-81
references.pmid: 20144603
references.citation: Neuron. 2003 Apr 10;38(1):17-31
references.pmid: 12691661
references.citation: Genes Dev. 1996 Jul 15;10(14):1751-62
references.pmid: 8698235
references.citation: Dev Biol. 2000 Nov 15;227(2):239-55
references.pmid: 11071752
references.citation: Dev Biol. 2005 Jan 1;277(1):155-69
references.pmid: 15572147
references.citation: Neuron. 1999 Aug;23(4):713-24
references.pmid: 10482238
references.citation: Development. 2007 Sep;134(18):3271-81
references.pmid: 17699610
references.citation: Development. 2006 Aug;133(15):2875-86
references.pmid: 16790476
references.citation: Pediatr Dev Pathol. 1999 Nov-Dec;2(6):559-69
references.pmid: 10508880