ZFIN ID: ZDB-PUB-121205-37
Schwann cell myelination requires Dynein function
Langworthy, M.M., and Appel, B.
Date: 2012
Source: Neural Development   7(1): 37 (Journal)
Registered Authors: Appel, Bruce, Langworthy, Melissa
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Cell Movement/genetics
  • Central Nervous System/cytology
  • Central Nervous System/metabolism
  • Colforsin/pharmacology
  • Cyclic AMP/metabolism
  • Cytoplasmic Dyneins/genetics
  • Cytoplasmic Dyneins/metabolism*
  • Demyelinating Diseases/genetics
  • Demyelinating Diseases/pathology*
  • Embryo, Nonmammalian/drug effects
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/genetics*
  • Green Fluorescent Proteins/genetics
  • Larva
  • Microscopy, Electron, Transmission
  • Morpholinos/pharmacology
  • Mutation/genetics
  • Myelin Basic Protein/metabolism
  • Myelin Sheath/metabolism
  • Myelin Sheath/pathology
  • Myelin Sheath/ultrastructure
  • Peripheral Nerves/metabolism
  • Peripheral Nerves/pathology
  • Peripheral Nerves/ultrastructure
  • RNA/metabolism
  • Schwann Cells/metabolism*
  • Schwann Cells/ultrastructure
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 23167977 Full text @ Neural Dev.


Interaction of Schwann cells with axons triggers signal transduction that drives expression of Pou3f1 and Egr2 transcription factors, which in turn promote myelination. Signal transduction appears to be mediated, at least in part, by cyclic adenosine monophosphate (cAMP) because elevation of cAMP levels can stimulate myelination in the absence of axon contact. The mechanisms by which the myelinating signal is conveyed remain unclear.


By analyzing mutations that disrupt myelination in zebrafish, we learned that Dynein cytoplasmic 1 heavy chain 1 (Dync1h1), which functions as a motor for intracellular molecular trafficking, is required for peripheral myelination. In dync1h1 mutants, Schwann cell progenitors migrated to peripheral nerves but then failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic experiments revealed that robust Myelin Basic Protein expression required Dync1h1 function within both Schwann cells and axons. Finally, treatment of dync1h1 mutants with a drug to elevate cAMP levels stimulated myelin gene expression.


Dync1h1 is required for retrograde transport in axons and mutations of Dync1h1 have been implicated in axon disease. Our data now provide evidence that Dync1h1 is also required for efficient myelination of peripheral axons by Schwann cells, perhaps by facilitating signal transduction necessary for myelination.