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Cited by 17Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationMicroRNA in disease regulation

Regulation of stem cell identity by miR-200a during spinal cord regeneration

Open access
Walker, Sarah E., Sabin, Keith Z., Gearhart, Micah D., Yamamoto, Kenta, Echeverri, Karen·2022·Development
DOI 10.1242/dev.200033PMC PMC8918811

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Abstract

Axolotls are an important model organism for multiple types of regeneration, including functional spinal cord regeneration. Remarkably, axolotls can repair their spinal cord after a small lesion injury and can also regenerate their entire tail following amputation. Several classical signaling pathways that are used during development are reactivated during regeneration, but how this is regulated remains a mystery. We have previously identified miR-200a as a key factor that promotes successful spinal cord regeneration. Here, using RNA-seq analysis, we discovered that the inhibition of miR-200a results in an upregulation of the classical mesodermal marker brachyury in spinal cord cells after injury. However, these cells still express the neural stem cell marker sox2. In vivo cell tracking allowed us to determine that these cells can give rise to cells of both the neural and mesoderm lineage. Additionally, we found that miR-200a can directly regulate brachyury via a seed sequence in the 3′UTR of the gene. Our data indicate that miR-200a represses mesodermal cell fate after a small lesion injury in the spinal cord when only glial cells and neurons need to be replaced.

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Authors
Walker, S. E., Sabin, K. Z., Gearhart, M. D., Yamamoto, K., & Echeverri, K.
Affiliations
  • Marine Biological Laboratory (US)
  • Stowers Institute for Medical Research (US)
  • University of Minnesota (US)
Corresponding author
Echeverri, Karen
ORCID
Venue
Development
Publisher
The Company of Biologists
Published
2022-02-01
Volume
149
Issue
3
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.200033
PMC
PMC8918811
OpenAlex
W4225453215
Cited by
17
References
2
Citations by year
2026: 1 · 2025: 6 · 2024: 2 · 2023: 2 · 2022: 6
FWCI
1.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Development (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Open Access Server of the Woods Hole Scientific Community (Woods Hole Scientific Community) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (T32 GM113846)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD092451)
  • Marine Biological Laboratory
  • Owens Family Foundation
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
miR-200a, spinal cord regeneration, axolotl, Brachyury, neural stem cells, SOX2, microRNA regulation, glial cells, neuronal replacement, cellular reprogramming
MeSH terms
Antagomirs, Brachyury Protein, Ambystoma mexicanum, Animals, Cell Differentiation, Fetal Proteins, Mesoderm, Neuroglia, Spinal Cord, Spinal Cord Injuries, Stem Cells, Tail, 3' Untranslated Regions, T-Box Domain Proteins, MicroRNAs, beta Catenin, SOXB1 Transcription Factors, Spinal Cord Regeneration, Neural Stem Cells, Wnt Signaling Pathway

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