The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells

Kośla, Katarzyna and Płuciennik, Elżbieta and Styczeń-Binkowska, Ewa and Nowakowska, Magdalena and Orzechowska, Magdalena and Bednarek, Andrzej K. (2019) The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells. Frontiers in Cellular Neuroscience, 13. ISSN 1662-5102

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Abstract

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 progenitor cell (hNPC) maintenance and how depletion of WWOX disturbs signaling pathways playing a pivotal role in neuronal differentiation and central nervous system (CNS) organogenesis. hNPC 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 cap analysis of gene expression (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.

Item Type: Article
Subjects: Souths Book > Medical Science
Depositing User: Unnamed user with email support@southsbook.com
Date Deposited: 26 May 2023 07:18
Last Modified: 02 Oct 2024 07:25
URI: http://research.europeanlibrarypress.com/id/eprint/993

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