ArticleProceedings of the National Academy of Sciences of the United States of America2005
Analysis of congenital hypomyelinating Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.
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171 citing papers in PubMed, 302 citations in OpenAlex.
- Myelination and Remyelination in Peripheral Nerve Injury: Mechanisms, Regulation, and Therapeutic Perspectives.MedComm · 2026Review
- Age-dependent effects of chronic traumatic and social isolation stress on mice social behavior.Neurobiology of stress · 2026Article
- Therapeutic effects of conditioned medium of immortalized dental pulp stem cells from human exfoliated deciduous teeth against experimental autoimmune neuritis.Scientific reports · 2025Article
- Actl6a regulates autophagy via Sox2-dependent Atg5 and Atg7 expression to inhibit apoptosis in spinal cord injury.Journal of advanced research · 2025Article
- Postnatal sustentacular cells as chromaffin progenitors and tumor cells of origin in VHL-related paragangliomas.NPJ precision oncology · 2025Article
- Article
- The STRIPAK complex is required for radial sorting and laminin receptor expression in Schwann cells.Cell reports · 2025Article
- Runx2 drives Schwann cells repair phenotype switch through chromatin remodeling and Sox2 activation after nerve injury.Molecular medicine (Cambridge, Mass.) · 2025Article
- Schwann cells in regeneration and cancer: an epithelial-mesenchymal transition perspective.Open biology · 2025Review
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- Pharmacologically targeting Schwann cells to improve regeneration following nerve damage.Frontiers in cell and developmental biology · 2025Review
- Role of theBiomedicines · 2024Article
- Transcription factor EGR2 alleviates autoimmune uveitis via activation of GDF15 to modulate the retinal microglial phenotype.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Schwann Cell Development and Myelination.Cold Spring Harbor perspectives in biology · 2024Review
- Enhancement of Heme-Oxygenase 1 in the Injured Peripheral Nerve Following Sulforaphane Administration Fosters Regeneration via Proliferation and Maintenance of Repair Schwann Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Peripheral Nervous System (PNS) Myelin Diseases.Cold Spring Harbor perspectives in biology · 2024Review
- Article
- Therapeutic Effect of an Ursolic Acid-Based Nutraceutical on Neuronal Regeneration after Sciatic Nerve Injury.International journal of molecular sciences · 2024Article
- Transcription Factor BCL11A Regulates Schwann Cell Behavior During Peripheral Nerve Regeneration.Molecular neurobiology · 2023Article
- Pathophysiology of Work-Related Neuropathies.Biomedicines · 2023Review
111 more citing papers are in PubMed but not listed here.
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6 authors at 1 institution in 1 country.
Funding
Abstract
Egr2 is a transcription factor required for peripheral nerve myelination in rodents, and mutations in Egr2 are associated with congenital hypomyelinating neuropathy (CHN) in humans. To further study its role in myelination, we generated mice harboring a hypomorphic Egr2 allele (Egr2Lo) that survive for up to 3 weeks postnatally, a period of active myelination in rodents. These Egr2Lo/Lo mice provided the opportunity to study the molecular effects of Egr2 deficiency on Schwann cell biology, an analysis that was not possible previously, because of the perinatal lethality of Egr2-null mice. Egr2Lo/Lo mice phenocopy CHN, as evidenced by the severe hypomyelination and increased numbers of proliferating Schwann cells of the peripheral nerves. Comparison of sciatic nerve gene expression profiles during development and after crush injury with those of Egr2Lo/Lo Schwann cells revealed that they are developmentally arrested, with down-regulation of myelination-related genes and up-regulation of genes associated with immature and promyelinating Schwann cells. One of the abnormally elevated genes in Egr2Lo/Lo Schwann cells, Sox2, encodes a transcription factor that is crucial for maintenance of neural stem cell pluripotency. Wild-type Schwann cells infected with Sox2 adenovirus or lentivirus inhibited expression of myelination-associated genes (e.g., myelin protein zero; Mpz), and failed to myelinate axons in vitro, but had an enhanced proliferative response to beta-neuregulin. The characterization of a mouse model of CHN has provided insight into Schwann cell differentiation and allowed the identification of Sox2 as a negative regulator of myelination.
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