The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells
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 ab...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00391/full |
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| author | Katarzyna Kośla Elżbieta Płuciennik Ewa Styczeń-Binkowska Magdalena Nowakowska Magdalena Orzechowska Andrzej K. Bednarek |
| author_facet | Katarzyna Kośla Elżbieta Płuciennik Ewa Styczeń-Binkowska Magdalena Nowakowska Magdalena Orzechowska Andrzej K. Bednarek |
| author_sort | Katarzyna Kośla |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T14:30:07Z |
| format | Article |
| id | doaj.art-ffe9f2cadf1541fb98fcc045b8916786 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-13T14:30:07Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-ffe9f2cadf1541fb98fcc045b89167862022-12-21T23:41:51ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-08-011310.3389/fncel.2019.00391454747The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor CellsKatarzyna KoślaElżbieta PłuciennikEwa Styczeń-BinkowskaMagdalena NowakowskaMagdalena OrzechowskaAndrzej K. BednarekThe 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.https://www.frontiersin.org/article/10.3389/fncel.2019.00391/fullWWOXneural progenitor cellsneuronal differentiationneurodegenerationWOREESCAR |
| spellingShingle | Katarzyna Kośla Elżbieta Płuciennik Ewa Styczeń-Binkowska Magdalena Nowakowska Magdalena Orzechowska Andrzej K. Bednarek The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells Frontiers in Cellular Neuroscience WWOX neural progenitor cells neuronal differentiation neurodegeneration WOREE SCAR |
| title | The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells |
| title_full | The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells |
| title_fullStr | The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells |
| title_full_unstemmed | The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells |
| title_short | The WWOX Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells |
| title_sort | wwox gene influences cellular pathways in the neuronal differentiation of human neural progenitor cells |
| topic | WWOX neural progenitor cells neuronal differentiation neurodegeneration WOREE SCAR |
| url | https://www.frontiersin.org/article/10.3389/fncel.2019.00391/full |
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