Desert Hedgehog Links Transcription Factor Sox10 to Perineurial Development
Copyright policy )Desert Hedgehog Links Transcription Factor Sox10 to Perineurial Development
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.Sox10deletion 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 ofDesert hedgehog(Dhh) in mice. Here we show that Sox10 activatesDhhexpression in Schwann cells via an enhancer that is located in intron 1 of theDhhgene. Sox10 binds this enhancer in monomeric form via several sites. Mutation of these sites abolishes both Schwann-cell-specific activity and Sox10 responsivenessin vitroand in transgenic mouse embryos. This argues that Sox10 activatesDhhexpression 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.
- University Medical Center Hamburg-Eppendorf Germany
- University of Erlangen-Nuremberg Germany
- Erasmus University Rotterdam Netherlands
Male, Chromatin Immunoprecipitation, SOXE Transcription Factors, Green Fluorescent Proteins, Gene Expression Regulation, Developmental, Mice, Transgenic, Exons, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Mutation, Peripheral Nervous System, Animals, Humans, EMC MGC-01-12-03, Hedgehog Proteins, Schwann Cells, RNA, Small Interfering, Cell Line, Transformed, Plant Proteins, Protein Binding
Male, Chromatin Immunoprecipitation, SOXE Transcription Factors, Green Fluorescent Proteins, Gene Expression Regulation, Developmental, Mice, Transgenic, Exons, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Mutation, Peripheral Nervous System, Animals, Humans, EMC MGC-01-12-03, Hedgehog Proteins, Schwann Cells, RNA, Small Interfering, Cell Line, Transformed, Plant Proteins, Protein Binding
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