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The transcription factor Sox10 is a key regulator of peripheral glial development17

The transcription factor Sox10 is a key regulator of peripheral glial development17
The transcription factor Sox10 is a key regulator of peripheral glial development17
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, but 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 Sox10(Dom) mice. Haploinsufficiency of Sox10 can thus cause pigmentation and megacolon defects, which are also observed in Sox10(Dom)/+ mice and in patients with Waardenburg-Hirschsprung disease caused by heterozygous SOX10 mutations.
neuroblastoma, transgenic, mice, research, physiology, motor neurons, high mobility group proteins, embryology, tumor cells, protein, nervous system, neural crest, patients, rats, ganglia, beta-galactosidase, cultured, transcription factors, research support, expression, inbred c57bl, knockout, gene expression regulation, metabolism, proteins, heterozygote, germany, down-regulation, animals, developmental, disease, pigmentation, genetics, neurons, cell differentiation, receptor, differentiation, dna-binding proteins, spinal, cytology, homozygote, erbb-3, mutation, neuroglia, chimera, phenotype
0890-9369
66-78
Britsch, S.
fc4ceb70-eed9-4596-8f8b-d02e1d81f9fb
Goerich, D.E.
320a2605-6e80-4624-a68e-c77a558a3220
Riethmacher, D.
1a0a0c2e-e94d-4d0a-a890-90107a2545bc
Peirano, R.I.
ecdf48f6-f30c-48c0-8bc0-0f37cdd2613a
Rossner, M.
65e752cf-9fa2-4b91-ae5e-73eb9732ae00
Nave, K.A.
f9379901-93f2-4576-b842-58bfa5b285b9
Birchmeier, C.
964c8c29-e585-408e-9257-288de2272ca8
Wegner, M.
5f266265-ae8e-4b0f-a9c1-a2dc0424ec55
Britsch, S.
fc4ceb70-eed9-4596-8f8b-d02e1d81f9fb
Goerich, D.E.
320a2605-6e80-4624-a68e-c77a558a3220
Riethmacher, D.
1a0a0c2e-e94d-4d0a-a890-90107a2545bc
Peirano, R.I.
ecdf48f6-f30c-48c0-8bc0-0f37cdd2613a
Rossner, M.
65e752cf-9fa2-4b91-ae5e-73eb9732ae00
Nave, K.A.
f9379901-93f2-4576-b842-58bfa5b285b9
Birchmeier, C.
964c8c29-e585-408e-9257-288de2272ca8
Wegner, M.
5f266265-ae8e-4b0f-a9c1-a2dc0424ec55

Britsch, S., Goerich, D.E., Riethmacher, D., Peirano, R.I., Rossner, M., Nave, K.A., Birchmeier, C. and Wegner, M. (2001) The transcription factor Sox10 is a key regulator of peripheral glial development17. Genes & Development, 15 (1), 66-78. (doi:10.1101/gad.186601).

Record type: Article

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, but 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 Sox10(Dom) mice. Haploinsufficiency of Sox10 can thus cause pigmentation and megacolon defects, which are also observed in Sox10(Dom)/+ mice and in patients with Waardenburg-Hirschsprung disease caused by heterozygous SOX10 mutations.

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More information

Published date: 1 January 2001
Keywords: neuroblastoma, transgenic, mice, research, physiology, motor neurons, high mobility group proteins, embryology, tumor cells, protein, nervous system, neural crest, patients, rats, ganglia, beta-galactosidase, cultured, transcription factors, research support, expression, inbred c57bl, knockout, gene expression regulation, metabolism, proteins, heterozygote, germany, down-regulation, animals, developmental, disease, pigmentation, genetics, neurons, cell differentiation, receptor, differentiation, dna-binding proteins, spinal, cytology, homozygote, erbb-3, mutation, neuroglia, chimera, phenotype

Identifiers

Local EPrints ID: 59523
URI: https://eprints.soton.ac.uk/id/eprint/59523
ISSN: 0890-9369
PURE UUID: 128d5610-c957-4341-9cf5-a8a45326725c
ORCID for D. Riethmacher: ORCID iD orcid.org/0000-0002-4206-5529

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Date deposited: 03 Sep 2008
Last modified: 15 Aug 2019 00:41

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Contributors

Author: S. Britsch
Author: D.E. Goerich
Author: D. Riethmacher ORCID iD
Author: R.I. Peirano
Author: M. Rossner
Author: K.A. Nave
Author: C. Birchmeier
Author: M. Wegner

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