Loss of Tiparp Results in Aberrant Layering of the Cerebral Cortex
| Autor: | Oleksandr Ievglevskyi, Joel C. Glover, Barbora Vagaska, Giulia Grimaldi, Elena Kondratskaya, Jason Matthews |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Biology
Development PARP 03 medical and health sciences Mice 0302 clinical medicine Neural Stem Cells Cell Movement medicine Animals heterocyclic compounds Progenitor cell GABAergic Neurons cortex layering Prefrontal cortex 030304 developmental biology Cell Proliferation Cerebral Cortex Mice Knockout 0303 health sciences Erratum/Corrigendum General Neuroscience Cell Cycle Wild type Tiparp 2.1 General Medicine New Research mono-ADP ribosylation Neural stem cell 3. Good health Cell biology Cortex (botany) medicine.anatomical_structure cortex post-translational modification Cerebral cortex Knockout mouse GABAergic Poly(ADP-ribose) Polymerases 030217 neurology & neurosurgery |
| Zdroj: | eNeuro |
| ISSN: | 2373-2822 |
| Popis: | 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose polymerase (TIPARP) is an enzyme that adds a single ADP-ribose moiety to itself or other proteins. Tiparp is highly expressed in the brain; however, its function in this organ is unknown. Here, we used Tiparp–/– mice to determine Tiparp’s role in the development of the prefrontal cortex. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose polymerase (TIPARP) is an enzyme that adds a single ADP-ribose moiety to itself or other proteins. Tiparp is highly expressed in the brain; however, its function in this organ is unknown. Here, we used Tiparp–/– mice to determine Tiparp’s role in the development of the prefrontal cortex. Loss of Tiparp resulted in an aberrant organization of the mouse cortex, where the upper layers presented increased cell density in the knock-out mice compared with wild type. Tiparp loss predominantly affected the correct distribution and number of GABAergic neurons. Furthermore, neural progenitor cell proliferation was significantly reduced. Neural stem cells (NSCs) derived from Tiparp–/– mice showed a slower rate of migration. Cytoskeletal components, such as α-tubulin are key regulators of neuronal differentiation and cortical development. α-tubulin mono-ADP ribosylation (MAR) levels were reduced in Tiparp–/– cells, suggesting that Tiparp plays a role in the MAR of α-tubulin. Despite the mild phenotype presented by Tiparp–/– mice, our findings reveal an important function for Tiparp and MAR in the correct development of the cortex. Unravelling Tiparp’s role in the cortex, could pave the way to a better understanding of a wide spectrum of neurological diseases which are known to have increased expression of TIPARP. |
| Databáze: | OpenAIRE |
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