Regulation, function and evolutionary structure of St18, encoding a Zinc-Finger Transcription Factor, in the oligodendrocyte lineage
Abstract
Myelinating oligodendrocytes are first observed during evolution in vertebrates above jawless fishes. Oligodendrocyte progenitor cells (OPCs) undergo extensive transcriptional and morphological remodelling to initiate differentiation and myelination. We report that the zinc-finger transcription factor St18 (aka Myt3) is upregulated during the OPC-to–newly formed oligodendrocyte (NFOL) transition. Single-nucleus RNA-sequencing (snRNA-seq) performed after lysolecithin-induced demyelination of the mouse spinal cord revealed that St18 was acutely upregulated in remyelinating OPCs. In primary rat OPC cultures, St18 overexpression promoted differentiation, whereas OPC conditional St18 knockout delayed developmental myelination in the mouse brain. Chromatin accessibility profiling identified candidate cis-regulatory elements for oligodendroglial St18 expression activated by core oligodendrocyte transcription factors, including SOX10, KLF9/13, and MYRF, and we confirmed that St18 expression in OPCs is Sox10-dependent in vivo. Phylogenetic analysis suggests that St18 arose via duplication of Myt1 in early jawed vertebrates, coinciding with the emergence of myelinating oligodendrocytes. These findings define St18 as a transcriptional marker of NFOLs and OLs and provide insight into the evolutionary regulation of central nervous system myelination.
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BibTeX
@misc{rowitch2026regulation,
title = {{Regulation, function and evolutionary structure of St18, encoding a Zinc-Finger Transcription Factor, in the oligodendrocyte lineage}},
author = {David Rowitch and Daniel Yamamoto and Adrien Vaquié and Tim Aberle and Michael Perry and Davod Shah and Diana Gold Diaz and Guy Lam and Zhaoyang Xu and Gregory Jordan and Gemma Girdler and Hannah Wüst and Laura Morcom and Aimee Wilson and Khalil Rawji and Penelope Dimas and Guoqiang Gu and Sarah Teichmann and Robin Franklin and Ragnhildur Káradóttir and Michael Wegner},
howpublished = {Research Square},
year = {2026},
month = oct,
doi = {10.21203/rs.3.rs-11211282/v1},
url = {https://doi.org/10.21203/rs.3.rs-11211282/v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Regulation, function and evolutionary structure of St18, encoding a Zinc-Finger Transcription Factor, in the oligodendrocyte lineage
AU - David Rowitch
AU - Daniel Yamamoto
AU - Adrien Vaquié
AU - Tim Aberle
AU - Michael Perry
AU - Davod Shah
AU - Diana Gold Diaz
AU - Guy Lam
AU - Zhaoyang Xu
AU - Gregory Jordan
AU - Gemma Girdler
AU - Hannah Wüst
AU - Laura Morcom
AU - Aimee Wilson
AU - Khalil Rawji
AU - Penelope Dimas
AU - Guoqiang Gu
AU - Sarah Teichmann
AU - Robin Franklin
AU - Ragnhildur Káradóttir
AU - Michael Wegner
PY - 2026
DA - 2026/10/29
PB - Research Square
DO - 10.21203/rs.3.rs-11211282/v1
UR - https://doi.org/10.21203/rs.3.rs-11211282/v1
AB - Myelinating oligodendrocytes are first observed during evolution in vertebrates above jawless fishes. Oligodendrocyte progenitor cells (OPCs) undergo extensive transcriptional and morphological remodelling to initiate differentiation and myelination. We report that the zinc-finger transcription factor St18 (aka Myt3) is upregulated during the OPC-to–newly formed oligodendrocyte (NFOL) transition. Single-nucleus RNA-sequencing (snRNA-seq) performed after lysolecithin-induced demyelination of the mouse spinal cord revealed that St18 was acutely upregulated in remyelinating OPCs. In primary rat OPC cultures, St18 overexpression promoted differentiation, whereas OPC conditional St18 knockout delayed developmental myelination in the mouse brain. Chromatin accessibility profiling identified candidate cis-regulatory elements for oligodendroglial St18 expression activated by core oligodendrocyte transcription factors, including SOX10, KLF9/13, and MYRF, and we confirmed that St18 expression in OPCs is Sox10-dependent in vivo. Phylogenetic analysis suggests that St18 arose via duplication of Myt1 in early jawed vertebrates, coinciding with the emergence of myelinating oligodendrocytes. These findings define St18 as a transcriptional marker of NFOLs and OLs and provide insight into the evolutionary regulation of central nervous system myelination.
SN - 2693-5015
ER -