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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neuroanat. | doi: 10.3389/fnana.2019.00075

Deprivation of Muscleblind-like proteins causes deficits in cortical neuron distribution and morphological changes in dendritic spines and postsynaptic densities

 Kuang-Yung Lee1, 2*, Ho-Ching Chang3, Carol Seah1 and  Li-Jen Lee3, 4, 5*
  • 1Department of Neurology, Keelung Chang Gung Memorial Hospital, Taiwan
  • 2College of Medicine, Chang Gung University, Taiwan
  • 3Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taiwan
  • 4Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taiwan
  • 5Neurobiology and Cognitive Science Center, National Taiwan University, Taiwan

Myotonic dystrophy (Dystrophia Myotonica; DM) is the most common adult onset muscular dystrophy and brain symptoms seriously affect patient’s quality of life. The Muscleblind-like (MBNL) proteins are splicing factors regulating posttranscriptional RNA during development. Previously, Mbnl KO mouse lines showed molecular and phenotypic evidences that recapitulating DM brains, however, detail morphological study has not yet been accomplished. In our studies, control (Mbnl1+/+; Mbnl2cond/cond; Nestin-Cre-/-), Mbnl2 conditional knockout (2KO, Mbnl1+/+; Mbnl2cond/cond; Nestin-Cre+/-) and Mbnl1/2 DKO (DKO, Mbnl1ΔE3/ΔE3; Mbnl2cond/cond; Nestin-Cre+/-) mice were generated by crossing three individual lines. Immunohistochemistry for evaluating densities and distributions of cortical neurons; Golgi staining for depicting the dendrites/dendritic spines; and electron microscopy for analyzing postsynaptic ultrastructure were performed. We found migratory defects in cortical neurons, reduction in dendritic complexity, immature dendritic spines and alterations of postsynaptic densities in the mutants. In conclusion, loss of function of Mbnl1/2 caused fundamental defects affecting neuronal positioning during migration, dendritic morphology and postsynaptic architectures that are reminiscent of predominantly immature and fetal phenotypes in DM patients.

Keywords: Muscleblind-like knockouts, Myotonic Dystrophy, Dendrites, Postsynaptic densities, cortical neurons, Interneurons

Received: 30 Apr 2019; Accepted: 11 Jul 2019.

Edited by:

Nicolas Heck, Université Pierre et Marie Curie, France

Reviewed by:

Richard Belvindrah, Sorbonne Universités, France
Mario Gomes-Pereira, Institut National de la Santé et de la Recherche Médicale (INSERM), France  

Copyright: © 2019 Lee, Chang, Seah and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Kuang-Yung Lee, Keelung Chang Gung Memorial Hospital, Department of Neurology, Keelung, Taiwan, kylee@cgmh.org.tw
Dr. Li-Jen Lee, Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taipei 100, Taiwan, ljlee@ntu.edu.tw