Mutations in dock1 disrupt early Schwann cell development

Rebecca L. Cunningham, Amy L. Herbert, Breanne L. Harty, Sarah D. Ackerman, Kelly Monk

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: In the peripheral nervous system (PNS), specialized glial cells called Schwann cells produce myelin, a lipid-rich insulating sheath that surrounds axons and promotes rapid action potential propagation. During development, Schwann cells must undergo extensive cytoskeletal rearrangements in order to become mature, myelinating Schwann cells. The intracellular mechanisms that drive Schwann cell development, myelination, and accompanying cell shape changes are poorly understood. Methods: Through a forward genetic screen in zebrafish, we identified a mutation in the atypical guanine nucleotide exchange factor, dock1, that results in decreased myelination of peripheral axons. Rescue experiments and complementation tests with newly engineered alleles confirmed that mutations in dock1 cause defects in myelination of the PNS. Whole mount in situ hybridization, transmission electron microscopy, and live imaging were used to fully define mutant phenotypes. Results: We show that Schwann cells in dock1 mutants can appropriately migrate and are not decreased in number, but exhibit delayed radial sorting and decreased myelination during early stages of development. Conclusions: Together, our results demonstrate that mutations in dock1 result in defects in Schwann cell development and myelination. Specifically, loss of dock1 delays radial sorting and myelination of peripheral axons in zebrafish.

Original languageEnglish (US)
Article number17
JournalNeural Development
Volume13
Issue number1
DOIs
StatePublished - Aug 8 2018

Fingerprint

Schwann Cells
Mutation
Axons
Peripheral Nervous System
Zebrafish
Genetic Complementation Test
Guanine Nucleotide Exchange Factors
Cell Shape
Myelin Sheath
Transmission Electron Microscopy
Neuroglia
Action Potentials
In Situ Hybridization
Alleles
Phenotype
Lipids

Keywords

  • dock1
  • Myelination
  • Schwann cell development
  • Zebrafish

ASJC Scopus subject areas

  • Developmental Neuroscience

Cite this

Cunningham, R. L., Herbert, A. L., Harty, B. L., Ackerman, S. D., & Monk, K. (2018). Mutations in dock1 disrupt early Schwann cell development. Neural Development, 13(1), [17]. https://doi.org/10.1186/s13064-018-0114-9

Mutations in dock1 disrupt early Schwann cell development. / Cunningham, Rebecca L.; Herbert, Amy L.; Harty, Breanne L.; Ackerman, Sarah D.; Monk, Kelly.

In: Neural Development, Vol. 13, No. 1, 17, 08.08.2018.

Research output: Contribution to journalArticle

Cunningham, RL, Herbert, AL, Harty, BL, Ackerman, SD & Monk, K 2018, 'Mutations in dock1 disrupt early Schwann cell development', Neural Development, vol. 13, no. 1, 17. https://doi.org/10.1186/s13064-018-0114-9
Cunningham, Rebecca L. ; Herbert, Amy L. ; Harty, Breanne L. ; Ackerman, Sarah D. ; Monk, Kelly. / Mutations in dock1 disrupt early Schwann cell development. In: Neural Development. 2018 ; Vol. 13, No. 1.
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