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

Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00391

The WWOX gene influences cellular pathways in the neuronal differentiation of human neural progenitor cells

 Katarzyna Kosla1*,  Elzbieta Płuciennik1, Ewa Styczen-Binkowska1, Magdalena Nowakowska1,  Magdalena Orzechowska1 and  Andrzej K. Bednarek1
  • 1Medical University of Lodz, Poland

The brain is the most functionally organized structure of all organs. It manages behavior, perception and higher cognitive functions. The WWOX gene is non classical tumor suppressor gene, which has been shown to have an impact on proliferation, apoptosis and migration processes. Moreover, genetic aberrations in WWOX induce severe neuropathological phenotypes in humans and rodents. The aim of the present study was to investigate in detail the impact of WWOX on human neural stem cell maintenance and how depletion of WWOX disturbs signaling pathways playing a pivotal role in neuronal differentiation and CNS organogenesis. Human neural stem cells with a silenced WWOX gene exhibited lowered mitochondrial redox potential, enhanced adhesion to fibronectin and extracellular matrix protein mixture, downregulation of MMP2/9 expression and impaired 3D growth. Global transcriptome analysis using CAGE found that WWOX downregulation significantly changes the expression of multiple genes engaged in cytoskeleton organization, adhesion, cell signaling and chromatin remodeling. The massive changes in gene expression caused by WWOX silencing may strongly affect the differentiation and migration of neurons in organogenesis, brain injury, cancerogenesis or neurodifferentiation. WWOX gene appears to be an important regulator of neural tissue architecture and function.

Keywords: WWOX, neuronal differentiation, neurodegeneration, WOREE, SCAR, CAGE, Neural progenitor cells (NPCs)

Received: 15 Feb 2019; Accepted: 08 Aug 2019.

Copyright: © 2019 Kosla, Płuciennik, Styczen-Binkowska, Nowakowska, Orzechowska and Bednarek. 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: PhD. Katarzyna Kosla, Medical University of Lodz, Lodz, Poland, katarzyna.kosla@umed.lodz.pl