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- Publisher Full Text
- Authors
- Küspert M
- Weider M
- Müller J
- Hermans-Borgmeyer I
- Meijer D
- Wegner M
- MESH
- Animals
- Cell Line, Transformed
- Chromatin Immunoprecipitation
- DNA-Binding Proteins
- Exons
- Gene Expression Regulation, Developmental
- Green Fluorescent Proteins
- Hedgehog Proteins
- Humans
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Mutation
- Peripheral Nervous System
- Plant Proteins
- Protein Binding
- RNA, Small Interfering
- SOXE Transcription Factors
- Schwann Cells
- Transfection
Abstract
Schwann cells are the main glial cell type in the PNS. They develop along nerves during embryogenesis and rely on the HMG domain containing Sox10 transcription factor for specification, lineage progression, and terminal differentiation. Sox10 deletion in immature Schwann cells caused peripheral nerve defects in mice that were not restricted to this glial cell type, although expression in the nerve and gene loss were. Formation of the perineurium as the protecting sheath was, for instance, heavily compromised. This resembled the defect observed after loss of Desert hedgehog (Dhh) in mice. Here we show that Sox10 activates Dhh expression in Schwann cells via an enhancer that is located in intron 1 of the Dhh gene. Sox10 binds this enhancer in monomeric form via several sites. Mutation of these sites abolishes both Schwann-cell-specific activity and Sox10 responsiveness in vitro and in transgenic mouse embryos. This argues that Sox10 activates Dhh expression by direct binding to the enhancer and by increasing Dhh levels promotes formation of the perineurial sheath. This represents the first mechanism for a non-cell-autonomous function of Sox10 during peripheral nerve development.
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Authors
Küspert M, Weider M, Müller J, Hermans-Borgmeyer I, Meijer D, Wegner M
Institution
Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, Germany.
Source
The Journal of neuroscience : the official journal of the Society for Neuroscience 32:16 2012 Apr 18 pg 5472-80MeSH
AnimalsCell Line, Transformed
Chromatin Immunoprecipitation
DNA-Binding Proteins
Exons
Gene Expression Regulation, Developmental
Green Fluorescent Proteins
Hedgehog Proteins
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation
Peripheral Nervous System
Plant Proteins
Protein Binding
RNA, Small Interfering
SOXE Transcription Factors
Schwann Cells
Transfection
Pub Type(s)
Journal ArticleResearch Support, Non-U.S. Gov't
Language
eng
PubMed ID
22514309