Sox10 is required for Schwann cell identity and progression beyond the immature Schwann cell stage

Markus Finzsch, Silke Schreiner, Tatjana Kichko, Peter Reeh, Ernst R Tamm, Michael R Bösl, Dies Meijer, Michael Wegner

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)701-12
Number of pages12
JournalJournal of Cell Biology
Volume189
Issue number4
DOIs
Publication statusPublished - 17 May 2010

Keywords

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Embryo, Mammalian
  • Mice
  • Mice, Transgenic
  • Mutation
  • Peripheral Nervous System Diseases
  • Rats
  • SOXE Transcription Factors
  • Schwann Cells

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