ZFIN ID: ZDB-PUB-180810-2
Mutations in dock1 disrupt early Schwann cell development
Cunningham, R.L., Herbert, A.L., Harty, B.L., Ackerman, S.D., Monk, K.R.
Date: 2018
Source: Neural Development 13: 17 (Journal)
Registered Authors: Monk, Kelly
Keywords: Myelination, Schwann cell development, Zebrafish, dock1
MeSH Terms:
  • Age Factors
  • Animals
  • Animals, Genetically Modified
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental/genetics*
  • Lateral Line System/cytology*
  • Lateral Line System/embryology
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Microinjections
  • Microscopy, Electron, Transmission
  • Mutation/genetics*
  • Myelin Basic Protein/metabolism
  • Peripheral Nervous System/cytology
  • Peripheral Nervous System/embryology
  • RNA, Messenger/metabolism
  • Schwann Cells/physiology*
  • Schwann Cells/ultrastructure
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • rac GTP-Binding Proteins/genetics*
  • rac GTP-Binding Proteins/metabolism
PubMed: 30089513 Full text @ Neural Dev.
FIGURES
ABSTRACT
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.
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.
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.
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.
ADDITIONAL INFORMATIONNo data available