Multiple roles of Id4 in developmental myelination: predicted outcomes and unexpected findings
Abstract
Myelination in the central nervous system is a complex process requiring the integration of oligodendrocyte progenitor differentiation and the coordinate expression of myelin genes. This study addresses the role of the helix-loop-helix protein Id4 in these two events. Overexpression of Id4 in oligodendrocyte progenitors prevents differentiation and consequently decreases the endogenous expression of all myelin genes. Conversely, progenitors lacking Id4 display precocious differentiation both in vitro and in vivo, and this phenotype is partially compensated by increased apoptosis. Besides this role, Id4 also has the ability to decrease the activity of specific myelin promoters, since Id4 overexpression decreases the activity of luciferase reporter genes driven by the ceramide galactosyltransferase (CGT) or myelin basic protein (MBP) promoter, but not by a myelin proteolipid protein (PLP) promoter. Consistent with these results, the expression levels of MBP and CGT are greater in neonatal Id4 null mice when compared with wild-type siblings and correlate with the early detection of MBP immunoreactive myelinated fibers. In contrast, the levels of other myelin proteins, such as PLP and myelin associated glycoprotein (MAG) are decreased in the Id4 null mice. MAG expression is localized to the soma rather than the fibers of immunoreactive cells in the neonatal brain and compensated at later developmental stages. These data support the role of Id4 as oligodendrocyte differentiation inhibitor with the ability to differentially regulate the expression and subcellular distribution of myelin gene products.
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The distal segment of the 2.2 kb human MAG promoter fragment contains binding sites for YY1 and Id4.
“The distal segment of this fragment contained binding sites for both positive and negative transcriptional regulators such as Yin Yang 1 (YY1) and Inhibitor of DNA Binding 4 (Id4; Marin-Husstege et al., 2006; He et al., 2007; Zolova and Wight, 2011).”
From Recombinant Human Myelin-Associated Glycoprotein Promoter Drives Selective AAV-Mediated Transgene Expression in Oligodendrocytes (2016) · cites this paper as Marin-Husstege et al., 2006
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- Authors
- Marin‐Husstege, M., He, Y., Li, J., Kondo, T., Sablitzky, F., & Casaccia‐Bonnefil, P.
- Affiliations
- University of Nottingham (GB)
- Corresponding author
- Sablitzky, Fred
- Casaccia‐Bonnefil, Patrizia
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2006-07-21
- Volume
- 54
- Issue
- 4
- Pages
- 285-296
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2039383073
- Cited by
- 91
- References
- 43
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 3 · 2022: 8 · 2021: 4 · 2020: 2 · 2019: 7 · 2018: 1 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 4
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- National Institute of Neurological Disorders and Stroke (R01NS042925, R01NS42925)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Id4, myelination, myelin gene expression, helix-loop-helix proteins, myelin basic protein, myelin-associated glycoprotein, proteolipid protein, apoptosis, central nervous system development
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Densitometry, Myelin Basic Protein, Immunohistochemistry, Luciferases, Mitogens, Myelin Sheath, Oligodendroglia, Promoter Regions, Genetic, Stem Cells, Thyroid Hormones, Transfection, Blotting, Western, Gene Expression, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, In Situ Nick-End Labeling, Mice, Inhibitor of Differentiation Proteins
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