Potential role of TGFΒ and autophagy in early crebellum development
During development, the interconnected generation of various neural cell types within the cerebellar primordium is essential. Over embryonic (E) days E9−E13, Purkinje cells (PCs), and cerebellar nuclei (CN) neurons are among the created primordial neurons. The molecular and cellular mechanisms funda...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580822001583 |
| _version_ | 1797997372812296192 |
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| author | Azadeh Dalvand Simone C. da Silva Rosa Saeid Ghavami Hassan Marzban |
| author_facet | Azadeh Dalvand Simone C. da Silva Rosa Saeid Ghavami Hassan Marzban |
| author_sort | Azadeh Dalvand |
| collection | DOAJ |
| description | During development, the interconnected generation of various neural cell types within the cerebellar primordium is essential. Over embryonic (E) days E9−E13, Purkinje cells (PCs), and cerebellar nuclei (CN) neurons are among the created primordial neurons. The molecular and cellular mechanisms fundamental for the early cerebellar neurogenesis, migration/differentiation, and connectivity are not clear yet. Autophagy has a vital role in controlling cellular phenotypes, such as epithelial-to-mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT). Transforming growth factor-beta 1 (TGF-β1) is the main player in pre-and postnatal development and controlling cellular morphological type via various mechanisms, such as autophagy. Thus, we hypothesized that TGF-β1 may regulate early cerebellar development by modifying the levels of cell adhesion molecules (CAMs) and consequently autophagy pathway in the mouse cerebellar primordium. We demonstrated the stimulation of the canonical TGF-β1 signaling pathway at the point that concurs with the generation of the nuclear transitory zone and PC plate in mice. Furthermore, our data show that the stimulated TGF-β1 signaling pathway progressively and chronologically could upregulate the expression of β-catenin (CTNNB1) and N-cadherin (CDH2) with the most expression at E11 and E12, leading to upregulation of chromodomain helicase DNA binding protein 8 (CDH8) and neural cell adhesion molecule 1 (NCAM1) expression, at E12 and E13. Finally, we demonstrated that the stimulated TGF-β signaling pathway may impede the autophagic flux at E11/E12. Nevertheless, basal autophagy flux happens at earlier developmental phases from E9−E10. Our study determined potential role of the TGF-β signaling and its regulatory impacts on autophagic flux during cerebellar development and cadherin expression, which can facilitate the proliferation, migration/differentiation, and placement of PCs and the CN neurons in their designated areas. |
| first_indexed | 2024-04-11T10:31:55Z |
| format | Article |
| id | doaj.art-ecf477b02b6c41a1be9c12c10c267865 |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-04-11T10:31:55Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-ecf477b02b6c41a1be9c12c10c2678652022-12-22T04:29:24ZengElsevierBiochemistry and Biophysics Reports2405-58082022-12-0132101358Potential role of TGFΒ and autophagy in early crebellum developmentAzadeh Dalvand0Simone C. da Silva Rosa1Saeid Ghavami2Hassan Marzban3Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Science, University of Manitoba, Winnipeg, MB, CanadaDepartment of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Science, University of Manitoba, Winnipeg, MB, CanadaCorresponding author.; Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Science, University of Manitoba, Winnipeg, MB, CanadaCorresponding author.; Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Science, University of Manitoba, Winnipeg, MB, CanadaDuring development, the interconnected generation of various neural cell types within the cerebellar primordium is essential. Over embryonic (E) days E9−E13, Purkinje cells (PCs), and cerebellar nuclei (CN) neurons are among the created primordial neurons. The molecular and cellular mechanisms fundamental for the early cerebellar neurogenesis, migration/differentiation, and connectivity are not clear yet. Autophagy has a vital role in controlling cellular phenotypes, such as epithelial-to-mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT). Transforming growth factor-beta 1 (TGF-β1) is the main player in pre-and postnatal development and controlling cellular morphological type via various mechanisms, such as autophagy. Thus, we hypothesized that TGF-β1 may regulate early cerebellar development by modifying the levels of cell adhesion molecules (CAMs) and consequently autophagy pathway in the mouse cerebellar primordium. We demonstrated the stimulation of the canonical TGF-β1 signaling pathway at the point that concurs with the generation of the nuclear transitory zone and PC plate in mice. Furthermore, our data show that the stimulated TGF-β1 signaling pathway progressively and chronologically could upregulate the expression of β-catenin (CTNNB1) and N-cadherin (CDH2) with the most expression at E11 and E12, leading to upregulation of chromodomain helicase DNA binding protein 8 (CDH8) and neural cell adhesion molecule 1 (NCAM1) expression, at E12 and E13. Finally, we demonstrated that the stimulated TGF-β signaling pathway may impede the autophagic flux at E11/E12. Nevertheless, basal autophagy flux happens at earlier developmental phases from E9−E10. Our study determined potential role of the TGF-β signaling and its regulatory impacts on autophagic flux during cerebellar development and cadherin expression, which can facilitate the proliferation, migration/differentiation, and placement of PCs and the CN neurons in their designated areas.http://www.sciencedirect.com/science/article/pii/S2405580822001583Cerebellum early developmentAutophagyAutophagy fluxTransforming growth factor-beta |
| spellingShingle | Azadeh Dalvand Simone C. da Silva Rosa Saeid Ghavami Hassan Marzban Potential role of TGFΒ and autophagy in early crebellum development Biochemistry and Biophysics Reports Cerebellum early development Autophagy Autophagy flux Transforming growth factor-beta |
| title | Potential role of TGFΒ and autophagy in early crebellum development |
| title_full | Potential role of TGFΒ and autophagy in early crebellum development |
| title_fullStr | Potential role of TGFΒ and autophagy in early crebellum development |
| title_full_unstemmed | Potential role of TGFΒ and autophagy in early crebellum development |
| title_short | Potential role of TGFΒ and autophagy in early crebellum development |
| title_sort | potential role of tgfβ and autophagy in early crebellum development |
| topic | Cerebellum early development Autophagy Autophagy flux Transforming growth factor-beta |
| url | http://www.sciencedirect.com/science/article/pii/S2405580822001583 |
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