Ketamine Modulates Zic5 Expression via the Notch Signaling Pathway in Neural Crest Induction
Ketamine is a potent dissociative anesthetic and the most commonly used illicit drug. Many addicts are women at childbearing age. Although ketamine has been extensively studied as a clinical anesthetic, its effects on embryonic development are poorly understood. Here, we applied the Xenopus model to...
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00009/full |
| _version_ | 1818609063863255040 |
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| author | Yu Shi Yu Shi Jiejing Li Chunjiang Chen Yongwu Xia Yongwu Xia Yanxi Li Pan Zhang Pan Zhang Ying Xu Tingyu Li Weihui Zhou Weihong Song Weihong Song |
| author_facet | Yu Shi Yu Shi Jiejing Li Chunjiang Chen Yongwu Xia Yongwu Xia Yanxi Li Pan Zhang Pan Zhang Ying Xu Tingyu Li Weihui Zhou Weihong Song Weihong Song |
| author_sort | Yu Shi |
| collection | DOAJ |
| description | Ketamine is a potent dissociative anesthetic and the most commonly used illicit drug. Many addicts are women at childbearing age. Although ketamine has been extensively studied as a clinical anesthetic, its effects on embryonic development are poorly understood. Here, we applied the Xenopus model to study the effects of ketamine on development. We found that exposure to ketamine from pre-gastrulation (stage 7) to early neural plate (stage 13.5) resulted in disruption of neural crest (NC) derivatives. Ketamine exposure did not affect mesoderm development as indicated by the normal expression of Chordin, Xbra, Wnt8, and Fgf8. However, ketamine treatment significantly inhibited Zic5 and Slug expression at early neural plate stage. Overexpression of Zic5 rescued ketamine-induced Slug inhibition, suggesting the blockage of NC induction was mediated by Zic5. Furthermore, we found Notch signaling was altered by ketamine. Ketamine inhibited the expression of Notch targeted genes including Hes5.2a, Hes5.2b, and ESR1 and ketamine-treated embryos exhibited Notch-deficient somite phenotypes. A 15 bp core binding element upstream of Zic5 was induced by Notch signaling and caused transcriptional activation. These results demonstrated that Zic5 works as a downstream target gene of Notch signaling in Xenopus NC induction. Our study provides a novel teratogenic mechanism whereby ketamine disrupts NC induction via targeting a Notch-Zic5 signaling pathway. |
| first_indexed | 2024-12-16T14:52:35Z |
| format | Article |
| id | doaj.art-2bb1616f7e36437cb27aa57e08ae11e2 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-16T14:52:35Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-2bb1616f7e36437cb27aa57e08ae11e22022-12-21T22:27:33ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-02-011110.3389/fnmol.2018.00009317378Ketamine Modulates Zic5 Expression via the Notch Signaling Pathway in Neural Crest InductionYu Shi0Yu Shi1Jiejing Li2Chunjiang Chen3Yongwu Xia4Yongwu Xia5Yanxi Li6Pan Zhang7Pan Zhang8Ying Xu9Tingyu Li10Weihui Zhou11Weihong Song12Weihong Song13Department of Clinical Laboratory, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Clinical Laboratory, The Affiliated Hospital of KMUST, Medical School, Kunming University of Science and Technology, Kunming, ChinaChongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Clinical Laboratory, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Anesthesiology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Anesthesiology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing City Key Lab of Translational Medical Research in Cognitive Development and Learning and Memory Disorders and Ministry of Education Key Lab of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaTownsend Family Laboratories, Department of Psychiatry, The University of British Columbia, Vancouver, BC, CanadaKetamine is a potent dissociative anesthetic and the most commonly used illicit drug. Many addicts are women at childbearing age. Although ketamine has been extensively studied as a clinical anesthetic, its effects on embryonic development are poorly understood. Here, we applied the Xenopus model to study the effects of ketamine on development. We found that exposure to ketamine from pre-gastrulation (stage 7) to early neural plate (stage 13.5) resulted in disruption of neural crest (NC) derivatives. Ketamine exposure did not affect mesoderm development as indicated by the normal expression of Chordin, Xbra, Wnt8, and Fgf8. However, ketamine treatment significantly inhibited Zic5 and Slug expression at early neural plate stage. Overexpression of Zic5 rescued ketamine-induced Slug inhibition, suggesting the blockage of NC induction was mediated by Zic5. Furthermore, we found Notch signaling was altered by ketamine. Ketamine inhibited the expression of Notch targeted genes including Hes5.2a, Hes5.2b, and ESR1 and ketamine-treated embryos exhibited Notch-deficient somite phenotypes. A 15 bp core binding element upstream of Zic5 was induced by Notch signaling and caused transcriptional activation. These results demonstrated that Zic5 works as a downstream target gene of Notch signaling in Xenopus NC induction. Our study provides a novel teratogenic mechanism whereby ketamine disrupts NC induction via targeting a Notch-Zic5 signaling pathway.http://journal.frontiersin.org/article/10.3389/fnmol.2018.00009/fullXenopusneural crestketamineNotchZic5 |
| spellingShingle | Yu Shi Yu Shi Jiejing Li Chunjiang Chen Yongwu Xia Yongwu Xia Yanxi Li Pan Zhang Pan Zhang Ying Xu Tingyu Li Weihui Zhou Weihong Song Weihong Song Ketamine Modulates Zic5 Expression via the Notch Signaling Pathway in Neural Crest Induction Frontiers in Molecular Neuroscience Xenopus neural crest ketamine Notch Zic5 |
| title | Ketamine Modulates Zic5 Expression via the Notch Signaling Pathway in Neural Crest Induction |
| title_full | Ketamine Modulates Zic5 Expression via the Notch Signaling Pathway in Neural Crest Induction |
| title_fullStr | Ketamine Modulates Zic5 Expression via the Notch Signaling Pathway in Neural Crest Induction |
| title_full_unstemmed | Ketamine Modulates Zic5 Expression via the Notch Signaling Pathway in Neural Crest Induction |
| title_short | Ketamine Modulates Zic5 Expression via the Notch Signaling Pathway in Neural Crest Induction |
| title_sort | ketamine modulates zic5 expression via the notch signaling pathway in neural crest induction |
| topic | Xenopus neural crest ketamine Notch Zic5 |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2018.00009/full |
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