Neural conditional ablation of the protein tyrosine phosphatase receptor Delta PTPRD impairs gliogenesis in the developing mouse brain cortex
Neurodevelopmental disorders are characterized by alterations in the development of the cerebral cortex, including aberrant changes in the number and function of neural cells. Although neurogenesis is one of the most studied cellular processes in these pathologies, little evidence is known about gli...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1357862/full |
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| author | Francisca Cornejo Nayhara Franchini Bastián I. Cortés Bastián I. Cortés Daniela Elgueta Gonzalo I. Cancino |
| author_facet | Francisca Cornejo Nayhara Franchini Bastián I. Cortés Bastián I. Cortés Daniela Elgueta Gonzalo I. Cancino |
| author_sort | Francisca Cornejo |
| collection | DOAJ |
| description | Neurodevelopmental disorders are characterized by alterations in the development of the cerebral cortex, including aberrant changes in the number and function of neural cells. Although neurogenesis is one of the most studied cellular processes in these pathologies, little evidence is known about glial development. Genetic association studies have identified several genes associated with neurodevelopmental disorders. Indeed, variations in the PTPRD gene have been associated with numerous brain disorders, including autism spectrum disorder, restless leg syndrome, and schizophrenia. We previously demonstrated that constitutive loss of PTPRD expression induces significant alterations in cortical neurogenesis, promoting an increase in intermediate progenitors and neurons in mice. However, its role in gliogenesis has not been evaluated. To assess this, we developed a conditional knockout mouse model lacking PTPRD expression in telencephalon cells. Here, we found that the lack of PTPRD in the mouse cortex reduces glial precursors, astrocytes, and oligodendrocytes. According to our results, this decrease in gliogenesis resulted from a reduced number of radial glia cells at gliogenesis onset and a lower gliogenic potential in cortical neural precursors due to less activation of the JAK/STAT pathway and reduced expression of gliogenic genes. Our study shows PTPRD as a regulator of the glial/neuronal balance during cortical neurodevelopment and highlights the importance of studying glial development to understand the etiology of neurodevelopmental diseases. |
| first_indexed | 2024-03-07T19:44:59Z |
| format | Article |
| id | doaj.art-f5881abd171146b8b06f93671c6a3d76 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-07T19:44:59Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-f5881abd171146b8b06f93671c6a3d762024-02-29T04:27:27ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-02-011210.3389/fcell.2024.13578621357862Neural conditional ablation of the protein tyrosine phosphatase receptor Delta PTPRD impairs gliogenesis in the developing mouse brain cortexFrancisca Cornejo0Nayhara Franchini1Bastián I. Cortés2Bastián I. Cortés3Daniela Elgueta4Gonzalo I. Cancino5Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, ChileCenter for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, ChileCenter for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, ChileDepartment of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, ChileDepartment of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, ChileDepartment of Cell and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, ChileNeurodevelopmental disorders are characterized by alterations in the development of the cerebral cortex, including aberrant changes in the number and function of neural cells. Although neurogenesis is one of the most studied cellular processes in these pathologies, little evidence is known about glial development. Genetic association studies have identified several genes associated with neurodevelopmental disorders. Indeed, variations in the PTPRD gene have been associated with numerous brain disorders, including autism spectrum disorder, restless leg syndrome, and schizophrenia. We previously demonstrated that constitutive loss of PTPRD expression induces significant alterations in cortical neurogenesis, promoting an increase in intermediate progenitors and neurons in mice. However, its role in gliogenesis has not been evaluated. To assess this, we developed a conditional knockout mouse model lacking PTPRD expression in telencephalon cells. Here, we found that the lack of PTPRD in the mouse cortex reduces glial precursors, astrocytes, and oligodendrocytes. According to our results, this decrease in gliogenesis resulted from a reduced number of radial glia cells at gliogenesis onset and a lower gliogenic potential in cortical neural precursors due to less activation of the JAK/STAT pathway and reduced expression of gliogenic genes. Our study shows PTPRD as a regulator of the glial/neuronal balance during cortical neurodevelopment and highlights the importance of studying glial development to understand the etiology of neurodevelopmental diseases.https://www.frontiersin.org/articles/10.3389/fcell.2024.1357862/fullgliogenesisgliabrain cortexPTPRDneural precursor cellsastrocytes |
| spellingShingle | Francisca Cornejo Nayhara Franchini Bastián I. Cortés Bastián I. Cortés Daniela Elgueta Gonzalo I. Cancino Neural conditional ablation of the protein tyrosine phosphatase receptor Delta PTPRD impairs gliogenesis in the developing mouse brain cortex Frontiers in Cell and Developmental Biology gliogenesis glia brain cortex PTPRD neural precursor cells astrocytes |
| title | Neural conditional ablation of the protein tyrosine phosphatase receptor Delta PTPRD impairs gliogenesis in the developing mouse brain cortex |
| title_full | Neural conditional ablation of the protein tyrosine phosphatase receptor Delta PTPRD impairs gliogenesis in the developing mouse brain cortex |
| title_fullStr | Neural conditional ablation of the protein tyrosine phosphatase receptor Delta PTPRD impairs gliogenesis in the developing mouse brain cortex |
| title_full_unstemmed | Neural conditional ablation of the protein tyrosine phosphatase receptor Delta PTPRD impairs gliogenesis in the developing mouse brain cortex |
| title_short | Neural conditional ablation of the protein tyrosine phosphatase receptor Delta PTPRD impairs gliogenesis in the developing mouse brain cortex |
| title_sort | neural conditional ablation of the protein tyrosine phosphatase receptor delta ptprd impairs gliogenesis in the developing mouse brain cortex |
| topic | gliogenesis glia brain cortex PTPRD neural precursor cells astrocytes |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1357862/full |
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