Cannabinoid Receptor 1 Regulates Zebrafish Renal Multiciliated Cell Development via cAMP Signaling
Endocannabinoid signaling plays a significant role in neurogenesis and nervous system physiology, but its roles in the development of other tissues are just beginning to be appreciated. Previous reports have shown the presence of the key endocannabinoid receptor Cannabinoid receptor 1 (CB1 or Cnr1)...
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MDPI AG
2025-06-01
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| Series: | Journal of Developmental Biology |
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| author | Thanh Khoa Nguyen Sophia Baker Julienne Angtuaco Liana Arceri Samuel Kaczor Bram Fitzsimonds Matthew R. Hawkins Rebecca A. Wingert |
| author_facet | Thanh Khoa Nguyen Sophia Baker Julienne Angtuaco Liana Arceri Samuel Kaczor Bram Fitzsimonds Matthew R. Hawkins Rebecca A. Wingert |
| author_sort | Thanh Khoa Nguyen |
| collection | DOAJ |
| description | Endocannabinoid signaling plays a significant role in neurogenesis and nervous system physiology, but its roles in the development of other tissues are just beginning to be appreciated. Previous reports have shown the presence of the key endocannabinoid receptor Cannabinoid receptor 1 (CB1 or Cnr1) in multiciliated (MCC) tissues and its upregulation in kidney diseases, yet the relationship between Cnr1 and renal MCC development is unknown. Here, we report that Cnr1 is essential for cilia development across tissues and regulates renal MCCs via cyclic AMP (cAMP) signaling during zebrafish embryogenesis. Using a combination of genetic and pharmacological studies, we found that the loss of function, agonism and antagonism of <i>cnr1</i> all lead to reduced mature renal MCC populations. <i>cnr1</i> deficiency also led to reduced cilia development across tissues, including the pronephros, ear, Kupffer’s vesicle (KV), and nasal placode. Interestingly, treatment with the cAMP activator Forskolin (FSK) restored renal MCC defects in agonist-treated embryos, suggesting that <i>cnr1</i> mediates cAMP signaling in renal MCC development. Meanwhile, treatment with the cAMP inhibitor SQ-22536 alone or with <i>cnr1</i> deficiency led to reduced MCC populations, suggesting that <i>cnr1</i> also mediates renal MCC development independently of cAMP signaling. Our findings indicate that <i>cnr1</i> has a critical role in controlling renal MCC development both via cAMP signaling and an independent pathway, further revealing implications for ciliopathies and renal diseases. |
| format | Article |
| id | doaj-art-78d8cdb2109b48a89fec4894d839bde0 |
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| issn | 2221-3759 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Journal of Developmental Biology |
| spelling | doaj-art-78d8cdb2109b48a89fec4894d839bde02025-06-25T13:59:16ZengMDPI AGJournal of Developmental Biology2221-37592025-06-011322010.3390/jdb13020020Cannabinoid Receptor 1 Regulates Zebrafish Renal Multiciliated Cell Development via cAMP SignalingThanh Khoa Nguyen0Sophia Baker1Julienne Angtuaco2Liana Arceri3Samuel Kaczor4Bram Fitzsimonds5Matthew R. Hawkins6Rebecca A. Wingert7Department of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USADepartment of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USADepartment of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USADepartment of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USADepartment of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USADepartment of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USADepartment of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USADepartment of Biological Sciences, Center for Stem Cells and Regenerative Medicine, Center for Zebrafish Research, University of Notre Dame, Notre Dame, IN 46556, USAEndocannabinoid signaling plays a significant role in neurogenesis and nervous system physiology, but its roles in the development of other tissues are just beginning to be appreciated. Previous reports have shown the presence of the key endocannabinoid receptor Cannabinoid receptor 1 (CB1 or Cnr1) in multiciliated (MCC) tissues and its upregulation in kidney diseases, yet the relationship between Cnr1 and renal MCC development is unknown. Here, we report that Cnr1 is essential for cilia development across tissues and regulates renal MCCs via cyclic AMP (cAMP) signaling during zebrafish embryogenesis. Using a combination of genetic and pharmacological studies, we found that the loss of function, agonism and antagonism of <i>cnr1</i> all lead to reduced mature renal MCC populations. <i>cnr1</i> deficiency also led to reduced cilia development across tissues, including the pronephros, ear, Kupffer’s vesicle (KV), and nasal placode. Interestingly, treatment with the cAMP activator Forskolin (FSK) restored renal MCC defects in agonist-treated embryos, suggesting that <i>cnr1</i> mediates cAMP signaling in renal MCC development. Meanwhile, treatment with the cAMP inhibitor SQ-22536 alone or with <i>cnr1</i> deficiency led to reduced MCC populations, suggesting that <i>cnr1</i> also mediates renal MCC development independently of cAMP signaling. Our findings indicate that <i>cnr1</i> has a critical role in controlling renal MCC development both via cAMP signaling and an independent pathway, further revealing implications for ciliopathies and renal diseases.https://www.mdpi.com/2221-3759/13/2/20multiciliated cellendocannabinoid pathwaycannabinoid receptorCnr1cAMP signalingkidney |
| spellingShingle | Thanh Khoa Nguyen Sophia Baker Julienne Angtuaco Liana Arceri Samuel Kaczor Bram Fitzsimonds Matthew R. Hawkins Rebecca A. Wingert Cannabinoid Receptor 1 Regulates Zebrafish Renal Multiciliated Cell Development via cAMP Signaling Journal of Developmental Biology multiciliated cell endocannabinoid pathway cannabinoid receptor Cnr1 cAMP signaling kidney |
| title | Cannabinoid Receptor 1 Regulates Zebrafish Renal Multiciliated Cell Development via cAMP Signaling |
| title_full | Cannabinoid Receptor 1 Regulates Zebrafish Renal Multiciliated Cell Development via cAMP Signaling |
| title_fullStr | Cannabinoid Receptor 1 Regulates Zebrafish Renal Multiciliated Cell Development via cAMP Signaling |
| title_full_unstemmed | Cannabinoid Receptor 1 Regulates Zebrafish Renal Multiciliated Cell Development via cAMP Signaling |
| title_short | Cannabinoid Receptor 1 Regulates Zebrafish Renal Multiciliated Cell Development via cAMP Signaling |
| title_sort | cannabinoid receptor 1 regulates zebrafish renal multiciliated cell development via camp signaling |
| topic | multiciliated cell endocannabinoid pathway cannabinoid receptor Cnr1 cAMP signaling kidney |
| url | https://www.mdpi.com/2221-3759/13/2/20 |
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