The transcription factor Sox10 is a key regulator of peripheral glial development

Stefan Britsch, Derk E. Goerich, Dieter Riethmacher, Reto I. Peirano, Moritz Rossner, Klaus Armin Nave, Carmen Birchmeier, Michael Wegner

Research output: Contribution to journalArticle

622 Citations (Scopus)

Abstract

The molecular mechanisms that determine glial cell fate in the vertebrate nervous system have not been elucidated. Peripheral glial cells differentiate from pluripotent neural crest cells. We show here that the transcription factor Sox10 is a key regulator in differentiation of peripheral glial cells. In mice that carry a spontaneous or a targeted mutation of Sox10, neuronal cells form in dorsal root ganglia, hut Schwann cells or satellite cells are not generated. At later developmental stages, this lack of peripheral glial cells results in a severe degeneration of sensory and motor neurons. Moreover, we show that Sox10 controls expression of ErbB3 in neural crest cells. ErbB3 encodes a Neuregulin receptor, and down-regulation of ErbB3 accounts for many changes in development of neural crest cells observed in Sox10 mutant mice. Sox10 also has functions not mediated by ErbB3, for instance in the melanocyte lineage. Phenotypes observed in heterozygous mice that carry a targeted Sox10 null allele reproduce those observed in heterozygous Sox10Dom mice. Haploinsufficiency of Sox10 can thus cause pigmentation and megacolon defects, which are also observed in Sox10Dom/+ mice and in patients with Waardenburg-Hirschsprung disease caused by heterozygous SOX10 mutations.

Original languageEnglish
Pages (from-to)66-78
Number of pages13
JournalGenes and Development
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 1 2001
Externally publishedYes

Fingerprint

Neuroglia
Transcription Factors
Neural Crest
Neuregulins
Megacolon
Haploinsufficiency
Mutation
Melanocytes
Schwann Cells
Pigmentation
Spinal Ganglia
Motor Neurons
Sensory Receptor Cells
Nervous System
Vertebrates
Down-Regulation
Alleles
Phenotype

Keywords

  • ErbB3
  • Glial cells
  • Melanocytes
  • Neural crest
  • Neuregulin
  • Sox10

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Britsch, S., Goerich, D. E., Riethmacher, D., Peirano, R. I., Rossner, M., Nave, K. A., ... Wegner, M. (2001). The transcription factor Sox10 is a key regulator of peripheral glial development. Genes and Development, 15(1), 66-78. https://doi.org/10.1101/gad.186601

The transcription factor Sox10 is a key regulator of peripheral glial development. / Britsch, Stefan; Goerich, Derk E.; Riethmacher, Dieter; Peirano, Reto I.; Rossner, Moritz; Nave, Klaus Armin; Birchmeier, Carmen; Wegner, Michael.

In: Genes and Development, Vol. 15, No. 1, 01.01.2001, p. 66-78.

Research output: Contribution to journalArticle

Britsch, S, Goerich, DE, Riethmacher, D, Peirano, RI, Rossner, M, Nave, KA, Birchmeier, C & Wegner, M 2001, 'The transcription factor Sox10 is a key regulator of peripheral glial development', Genes and Development, vol. 15, no. 1, pp. 66-78. https://doi.org/10.1101/gad.186601
Britsch, Stefan ; Goerich, Derk E. ; Riethmacher, Dieter ; Peirano, Reto I. ; Rossner, Moritz ; Nave, Klaus Armin ; Birchmeier, Carmen ; Wegner, Michael. / The transcription factor Sox10 is a key regulator of peripheral glial development. In: Genes and Development. 2001 ; Vol. 15, No. 1. pp. 66-78.
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