PUBLICATION
Mutations in dock1 disrupt early Schwann cell development
- Authors
- Cunningham, R.L., Herbert, A.L., Harty, B.L., Ackerman, S.D., Monk, K.R.
- ID
- ZDB-PUB-180810-2
- Date
- 2018
- Source
- Neural Development 13: 17 (Journal)
- Registered Authors
- Monk, Kelly
- Keywords
- Myelination, Schwann cell development, Zebrafish, dock1
- MeSH Terms
-
- Mutation/genetics*
- Schwann Cells/physiology*
- Schwann Cells/ultrastructure
- Peripheral Nervous System/cytology
- Peripheral Nervous System/embryology
- Gene Expression Regulation, Developmental/genetics*
- Microscopy, Electron, Transmission
- RNA, Messenger/metabolism
- Zebrafish
- Luminescent Proteins/genetics
- Luminescent Proteins/metabolism
- Animals
- Lateral Line System/cytology*
- Lateral Line System/embryology
- rac GTP-Binding Proteins/genetics*
- rac GTP-Binding Proteins/metabolism
- Age Factors
- Embryo, Nonmammalian
- Animals, Genetically Modified
- Myelin Basic Protein/metabolism
- Microinjections
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 30089513 Full text @ Neural Dev.
Citation
Cunningham, R.L., Herbert, A.L., Harty, B.L., Ackerman, S.D., Monk, K.R. (2018) Mutations in dock1 disrupt early Schwann cell development. Neural Development. 13:17.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping