Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6271261 | Neuroscience | 2016 | 34 Pages |
Abstract
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 gle1â/â mutant zebrafish display various aspects of LCCS, showing severe developmental abnormalities including motor neuron arborization 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 gle1â/â 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.
Keywords
NPColigodendrocyte lineage transcription factor 2Dbp5Anterior lateral line nervePosterior lateral line nervePIP2ALLNIP6MBPOlig2RNP5-ethynyl-2′-deoxyuridineEdUInositol hexakisphosphatespinal muscular atrophyamyotrophic lateral sclerosisTemALSSMACNSribonucleoproteincentral nervous systemphosphatidylinositol-4,5-bisphosphatenuclear pore complexZebrafish modelTransmission electron microscopyMotor neuronMyelin basic protein
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Authors
A. Seytanoglu, N.I. Alsomali, C.F. Valori, A. McGown, H.R. Kim, K. Ning, T. Ramesh, B. Sharrack, J.D. Wood, M. Azzouz,