Desert hedgehog links transcription factor Sox10 to perineurial development.
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Desert hedgehog links transcription factor Sox10 to perineurial development. / Küspert, Melanie; Weider, Matthias; Müller, Jana; Hermans-Borgmeyer, Irmgard; Meijer, Dies; Wegner, Michael.
In: J NEUROSCI, Vol. 32, No. 16, 16, 2012, p. 5472-5480.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Desert hedgehog links transcription factor Sox10 to perineurial development.
AU - Küspert, Melanie
AU - Weider, Matthias
AU - Müller, Jana
AU - Hermans-Borgmeyer, Irmgard
AU - Meijer, Dies
AU - Wegner, Michael
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Transfection
KW - Chromatin Immunoprecipitation
KW - Mutation/genetics
KW - RNA, Small Interfering/genetics/metabolism
KW - Cell Line, Transformed
KW - Green Fluorescent Proteins/genetics
KW - Schwann Cells/metabolism
KW - Gene Expression Regulation, Developmental/genetics/physiology
KW - Protein Binding/genetics
KW - Hedgehog Proteins/genetics/metabolism
KW - Exons/genetics
KW - DNA-Binding Proteins/genetics/metabolism
KW - Peripheral Nervous System/cytology/embryology/metabolism
KW - Plant Proteins/genetics/metabolism
KW - SOXE Transcription Factors/genetics/metabolism
KW - Animals
KW - Humans
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - Transfection
KW - Chromatin Immunoprecipitation
KW - Mutation/genetics
KW - RNA, Small Interfering/genetics/metabolism
KW - Cell Line, Transformed
KW - Green Fluorescent Proteins/genetics
KW - Schwann Cells/metabolism
KW - Gene Expression Regulation, Developmental/genetics/physiology
KW - Protein Binding/genetics
KW - Hedgehog Proteins/genetics/metabolism
KW - Exons/genetics
KW - DNA-Binding Proteins/genetics/metabolism
KW - Peripheral Nervous System/cytology/embryology/metabolism
KW - Plant Proteins/genetics/metabolism
KW - SOXE Transcription Factors/genetics/metabolism
M3 - SCORING: Journal article
VL - 32
SP - 5472
EP - 5480
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 16
M1 - 16
ER -