Embryonic Ethanol but Not Cannabinoid Exposure Affects Zebrafish Cardiac Development via Agrin and Sonic Hedgehog Interaction
Recent studies demonstrate the adverse effects of cannabinoids on development, including via pathways shared with ethanol exposure. Our laboratory has shown that both the nervous system and cardiac development are dependent on agrin modulation of sonic hedgehog (shh) and fibroblast growth factor (Fg...
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MDPI AG
2023-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/9/1327 |
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| author | Chengjin Zhang Natalie Ezem Shanta Mackinnon Gregory J. Cole |
| author_facet | Chengjin Zhang Natalie Ezem Shanta Mackinnon Gregory J. Cole |
| author_sort | Chengjin Zhang |
| collection | DOAJ |
| description | Recent studies demonstrate the adverse effects of cannabinoids on development, including via pathways shared with ethanol exposure. Our laboratory has shown that both the nervous system and cardiac development are dependent on agrin modulation of sonic hedgehog (shh) and fibroblast growth factor (Fgf) signaling pathways. As both ethanol and cannabinoids impact these signaling molecules, we examined their role on zebrafish heart development. Zebrafish embryos were exposed to a range of ethanol and/or cannabinoid receptor 1 and 2 agonist concentrations in the absence or presence of morpholino oligonucleotides that disrupt <i>agrin</i> or <i>shh</i> expression. In situ hybridization was employed to analyze cardiac marker gene expression. Exposure to cannabinoid receptor agonists disrupted midbrain–hindbrain boundary development, but had no effect on heart development, as assessed by the presence of cardiac edema or the altered expression of cardiac marker genes. In contrast, exposure to 1.5% ethanol induced cardiac edema and the altered expression of cardiac marker genes. Combined exposure to <i>agrin</i> or <i>shh</i> morpholino and 0.5% ethanol disrupted the <i>cmlc2</i> gene expression pattern, with the restoration of the normal expression following <i>shh</i> mRNA overexpression. These studies provide evidence that signaling pathways critical to heart development are sensitive to ethanol exposure<b>,</b> but not cannabinoid<b>s,</b> during early zebrafish embryogenesis. |
| first_indexed | 2024-03-11T04:21:12Z |
| format | Article |
| id | doaj.art-7515896e367e4b909f2c85c2c7886a7d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T04:21:12Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7515896e367e4b909f2c85c2c7886a7d2023-11-17T22:44:23ZengMDPI AGCells2073-44092023-05-01129132710.3390/cells12091327Embryonic Ethanol but Not Cannabinoid Exposure Affects Zebrafish Cardiac Development via Agrin and Sonic Hedgehog InteractionChengjin Zhang0Natalie Ezem1Shanta Mackinnon2Gregory J. Cole3Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USADuke-NCCU Summer Scholars Program, Duke University, Durham, NC 27708, USAJulius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USAJulius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USARecent studies demonstrate the adverse effects of cannabinoids on development, including via pathways shared with ethanol exposure. Our laboratory has shown that both the nervous system and cardiac development are dependent on agrin modulation of sonic hedgehog (shh) and fibroblast growth factor (Fgf) signaling pathways. As both ethanol and cannabinoids impact these signaling molecules, we examined their role on zebrafish heart development. Zebrafish embryos were exposed to a range of ethanol and/or cannabinoid receptor 1 and 2 agonist concentrations in the absence or presence of morpholino oligonucleotides that disrupt <i>agrin</i> or <i>shh</i> expression. In situ hybridization was employed to analyze cardiac marker gene expression. Exposure to cannabinoid receptor agonists disrupted midbrain–hindbrain boundary development, but had no effect on heart development, as assessed by the presence of cardiac edema or the altered expression of cardiac marker genes. In contrast, exposure to 1.5% ethanol induced cardiac edema and the altered expression of cardiac marker genes. Combined exposure to <i>agrin</i> or <i>shh</i> morpholino and 0.5% ethanol disrupted the <i>cmlc2</i> gene expression pattern, with the restoration of the normal expression following <i>shh</i> mRNA overexpression. These studies provide evidence that signaling pathways critical to heart development are sensitive to ethanol exposure<b>,</b> but not cannabinoid<b>s,</b> during early zebrafish embryogenesis.https://www.mdpi.com/2073-4409/12/9/1327cannabinoid<i>shh</i><i>agrin</i>FASDethanol |
| spellingShingle | Chengjin Zhang Natalie Ezem Shanta Mackinnon Gregory J. Cole Embryonic Ethanol but Not Cannabinoid Exposure Affects Zebrafish Cardiac Development via Agrin and Sonic Hedgehog Interaction Cells cannabinoid <i>shh</i> <i>agrin</i> FASD ethanol |
| title | Embryonic Ethanol but Not Cannabinoid Exposure Affects Zebrafish Cardiac Development via Agrin and Sonic Hedgehog Interaction |
| title_full | Embryonic Ethanol but Not Cannabinoid Exposure Affects Zebrafish Cardiac Development via Agrin and Sonic Hedgehog Interaction |
| title_fullStr | Embryonic Ethanol but Not Cannabinoid Exposure Affects Zebrafish Cardiac Development via Agrin and Sonic Hedgehog Interaction |
| title_full_unstemmed | Embryonic Ethanol but Not Cannabinoid Exposure Affects Zebrafish Cardiac Development via Agrin and Sonic Hedgehog Interaction |
| title_short | Embryonic Ethanol but Not Cannabinoid Exposure Affects Zebrafish Cardiac Development via Agrin and Sonic Hedgehog Interaction |
| title_sort | embryonic ethanol but not cannabinoid exposure affects zebrafish cardiac development via agrin and sonic hedgehog interaction |
| topic | cannabinoid <i>shh</i> <i>agrin</i> FASD ethanol |
| url | https://www.mdpi.com/2073-4409/12/9/1327 |
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