Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo

Seytanoglu, A., Alsomali, N.I., Valori, C.F., McGown, A., Kim, H.R., Ning, K., Ramesh, T., Sharrack, B., Wood, J.D., Azzouz, M.
Neuroscience   322: 287-97 (Journal)
Registered Authors
McGown, Alexander
Lethal congenital contracture syndrome 1, Motor neuron, Schwann cell development, Zebrafish model
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Arthrogryposis
  • Cell Differentiation/physiology
  • Cell Proliferation/physiology
  • Eye/embryology
  • Eye/pathology
  • Immunohistochemistry
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Microscopy, Electron, Transmission
  • Motor Neurons/pathology
  • Motor Neurons/physiology
  • Myelin Basic Protein/metabolism
  • Neural Stem Cells/pathology
  • Neural Stem Cells/physiology
  • RNA-Binding Proteins/genetics
  • Rhombencephalon/embryology
  • Rhombencephalon/pathology
  • Schwann Cells/pathology
  • Schwann Cells/physiology*
  • Survival Analysis
  • Zebrafish/embryology*
  • Zebrafish Proteins/deficiency*
  • Zebrafish Proteins/genetics
26921650 Full text @ Neuroscience
GLE1 mutations cause lethal congenital contracture syndrome 1 (LCCS1), a severe autosomal recessive fetal motor neuron disease, and more recently have been associated with amyotrophic lateral sclerosis (ALS). The gene encodes a highly conserved protein with an essential role in mRNA export. The mechanism linking Gle1 function to motor neuron degeneration in humans has not been elucidated, but increasing evidence implicates abnormal RNA processing as a key event in the pathogenesis of several motor neuron diseases. Homozygous gle1(-/-) mutant zebrafish display various aspects of LCCS, showing severe developmental abnormalities including motor neuron arborisation defects and embryonic lethality. A previous gene expression study on spinal cord from LCCS fetuses indicated that oligodendrocyte dysfunction may be an important factor in LCCS. We therefore set out to investigate the development of myelinating glia in gle1(-/-) mutant zebrafish embryos. While expression of myelin basic protein (mbp) in hindbrain oligodendrocytes appeared relatively normal, our studies revealed a prominent defect in Schwann cell precursor proliferation and differentiation in the posterior lateral line nerve. Other genes mutated in LCCS have important roles in Schwann cell development, thereby suggesting that Schwann cell deficits may be a common factor in LCCS pathogenesis. These findings illustrate the potential importance of glial cells such as myelinating Schwann cells in motor neuron diseases linked to RNA processing defects.
Genes / Markers
Show all Figures
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes