Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model
During embryonic spinal cord development, neural progenitor cells (NPCs) generate three major cell lines: neurons, oligodendrocytes, and astrocytes at precise times and locations within the spinal cord. Recent studies demonstrate early astrogenesis in animal models of spina bifida, which may play a...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.888351/full |
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| author | Marc Oria Marc Oria Bedika Pathak Zhen Li Kenan Bakri Kara Gouwens Maria Florencia Varela Kristin Lampe Kendall P. Murphy Kendall P. Murphy Chia-Ying Lin Jose L. Peiro Jose L. Peiro |
| author_facet | Marc Oria Marc Oria Bedika Pathak Zhen Li Kenan Bakri Kara Gouwens Maria Florencia Varela Kristin Lampe Kendall P. Murphy Kendall P. Murphy Chia-Ying Lin Jose L. Peiro Jose L. Peiro |
| author_sort | Marc Oria |
| collection | DOAJ |
| description | During embryonic spinal cord development, neural progenitor cells (NPCs) generate three major cell lines: neurons, oligodendrocytes, and astrocytes at precise times and locations within the spinal cord. Recent studies demonstrate early astrogenesis in animal models of spina bifida, which may play a role in neuronal dysfunction associated with this condition. However, to date, the pathophysiological mechanisms related to this early astrocytic response in spina bifida are poorly understood. This study aimed to characterize the development of early astrogliosis over time from Pax6+, Olig2+, or Nkx2.2+ NPCs using a retinoic acid-induced spina bifida rat model. At three gestational ages (E15, E17, and E20), spinal cords from fetuses with retinoic acid-induced spina bifida, their healthy sibling controls, or fetuses treated with the vehicle control were analyzed. Results indicated that premature astrogliosis and astrocytic activation were associated with an altered presence of Pax6+, Olig2+, and Nkx2.2+ NPCs in the lesion compared to the controls. Finally, this response correlated with an elevation in genes involved in the Notch-BMP signaling pathway. Taken together, changes in NPC patterning factor expression with Notch-BMP signaling upregulation may be responsible for the altered astrogenesis patterns observed in the spinal cord in a retinoic acid-induced spina bifida model. |
| first_indexed | 2024-12-12T10:00:31Z |
| format | Article |
| id | doaj.art-8beb6029f1d548db8a755ede0d6d6629 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-12T10:00:31Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-8beb6029f1d548db8a755ede0d6d66292022-12-22T00:28:00ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-06-011510.3389/fnmol.2022.888351888351Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat ModelMarc Oria0Marc Oria1Bedika Pathak2Zhen Li3Kenan Bakri4Kara Gouwens5Maria Florencia Varela6Kristin Lampe7Kendall P. Murphy8Kendall P. Murphy9Chia-Ying Lin10Jose L. Peiro11Jose L. Peiro12Center for Fetal and Placental Research, Cincinnati Children’s Hospital Medical Center (CCHMC), Cincinnati, OH, United StatesDepartment of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH, United StatesCenter for Fetal and Placental Research, Cincinnati Children’s Hospital Medical Center (CCHMC), Cincinnati, OH, United StatesCenter for Fetal and Placental Research, Cincinnati Children’s Hospital Medical Center (CCHMC), Cincinnati, OH, United StatesCenter for Fetal and Placental Research, Cincinnati Children’s Hospital Medical Center (CCHMC), Cincinnati, OH, United StatesCenter for Fetal and Placental Research, Cincinnati Children’s Hospital Medical Center (CCHMC), Cincinnati, OH, United StatesCenter for Fetal and Placental Research, Cincinnati Children’s Hospital Medical Center (CCHMC), Cincinnati, OH, United StatesCenter for Fetal and Placental Research, Cincinnati Children’s Hospital Medical Center (CCHMC), Cincinnati, OH, United StatesCenter for Fetal and Placental Research, Cincinnati Children’s Hospital Medical Center (CCHMC), Cincinnati, OH, United StatesDepartment of Orthopaedic Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH, United StatesDepartment of Orthopaedic Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH, United StatesCenter for Fetal and Placental Research, Cincinnati Children’s Hospital Medical Center (CCHMC), Cincinnati, OH, United StatesDepartment of Surgery, College of Medicine, University of Cincinnati, Cincinnati, OH, United StatesDuring embryonic spinal cord development, neural progenitor cells (NPCs) generate three major cell lines: neurons, oligodendrocytes, and astrocytes at precise times and locations within the spinal cord. Recent studies demonstrate early astrogenesis in animal models of spina bifida, which may play a role in neuronal dysfunction associated with this condition. However, to date, the pathophysiological mechanisms related to this early astrocytic response in spina bifida are poorly understood. This study aimed to characterize the development of early astrogliosis over time from Pax6+, Olig2+, or Nkx2.2+ NPCs using a retinoic acid-induced spina bifida rat model. At three gestational ages (E15, E17, and E20), spinal cords from fetuses with retinoic acid-induced spina bifida, their healthy sibling controls, or fetuses treated with the vehicle control were analyzed. Results indicated that premature astrogliosis and astrocytic activation were associated with an altered presence of Pax6+, Olig2+, and Nkx2.2+ NPCs in the lesion compared to the controls. Finally, this response correlated with an elevation in genes involved in the Notch-BMP signaling pathway. Taken together, changes in NPC patterning factor expression with Notch-BMP signaling upregulation may be responsible for the altered astrogenesis patterns observed in the spinal cord in a retinoic acid-induced spina bifida model.https://www.frontiersin.org/articles/10.3389/fnmol.2022.888351/fullneural tube defect (NTD)spina bifida (SB)neural progenitor cell (NPC)astrogenesisPax6Olig2 |
| spellingShingle | Marc Oria Marc Oria Bedika Pathak Zhen Li Kenan Bakri Kara Gouwens Maria Florencia Varela Kristin Lampe Kendall P. Murphy Kendall P. Murphy Chia-Ying Lin Jose L. Peiro Jose L. Peiro Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model Frontiers in Molecular Neuroscience neural tube defect (NTD) spina bifida (SB) neural progenitor cell (NPC) astrogenesis Pax6 Olig2 |
| title | Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model |
| title_full | Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model |
| title_fullStr | Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model |
| title_full_unstemmed | Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model |
| title_short | Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model |
| title_sort | premature neural progenitor cell differentiation into astrocytes in retinoic acid induced spina bifida rat model |
| topic | neural tube defect (NTD) spina bifida (SB) neural progenitor cell (NPC) astrogenesis Pax6 Olig2 |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.888351/full |
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