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. 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.
Institute of Biochemistry, Emil-Fischer-Zentrum, Friedrich-Alexander University Erlangen-Nürnberg, D-91054 Erlangen, Germany.
SourceThe Journal of neuroscience : the official journal of the Society for Neuroscience 32:16 2012 Apr 18 pg 5472-80
Cell Line, Transformed
Gene Expression Regulation, Developmental
Green Fluorescent Proteins
Mice, Inbred C57BL
Peripheral Nervous System
RNA, Small Interfering
SOXE Transcription Factors
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't