Proapoptotic <i>Bad</i> Involved in Brain Development, When Severely Defected, Induces Dramatic Malformation in Zebrafish
The BH3-only molecule Bad regulates cell death via its differential protein phosphorylation, but very few studies address its effect on early embryonic development in vertebrate systems. In this work, we examined the novel role of zebrafish Bad in the initial programmed cell death (PCD) for brain mo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/9/4832 |
| _version_ | 1797535404313804800 |
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| author | Jo-Chi Hung Jen-Leih Wu Jiann-Ruey Hong |
| author_facet | Jo-Chi Hung Jen-Leih Wu Jiann-Ruey Hong |
| author_sort | Jo-Chi Hung |
| collection | DOAJ |
| description | The BH3-only molecule Bad regulates cell death via its differential protein phosphorylation, but very few studies address its effect on early embryonic development in vertebrate systems. In this work, we examined the novel role of zebrafish Bad in the initial programmed cell death (PCD) for brain morphogenesis through reducing environmental stress and cell death signaling. Bad was considered to be a material factor that because of the knockdown of Bad by morpholino oligonucleotides, PCD was increased and the reactive oxygen species (ROS) level was enhanced, which correlated to trigger a p53/caspase-8 involving cell death signaling. This Bad knockdown-mediated environmental stress and enhanced cell dying can delay normal cell migration in the formation of the three germ layers, especially the ectoderm, for further brain development. Furthermore, Bad defects involved in three-germ-layers development at 8 hpf were identified by in situ hybridization approach on <i>cyp26</i>, <i>rtla</i>, and <i>Sox17</i> pattern expression markers. Finally, the Bad knockdown-induced severely defected brain was examined by tissue section from 24 to 48 h postfertilization (hpf), which correlated to induce dramatic malformation in the hindbrain. Our data suggest that the BH3-only molecule Bad regulates brain development via controlling programmed cell death on overcoming environmental stress for reducing secondary cell death signaling, which suggests that correlates to brain developmental and neurological disorders in this model system. |
| first_indexed | 2024-03-10T11:43:59Z |
| format | Article |
| id | doaj.art-0e9c5eceb0b841038dc4992b0d969a15 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:43:59Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0e9c5eceb0b841038dc4992b0d969a152023-11-21T18:13:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01229483210.3390/ijms22094832Proapoptotic <i>Bad</i> Involved in Brain Development, When Severely Defected, Induces Dramatic Malformation in ZebrafishJo-Chi Hung0Jen-Leih Wu1Jiann-Ruey Hong2Laboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng Kung University, Tainan 701, TaiwanLaboratory of Marine Molecular Biology and Biotechnology, Institute of Cellular and Organismic Biology, Academia Sinica, Nankang, Taipei 115, TaiwanLaboratory of Molecular Virology and Biotechnology, Institute of Biotechnology, National Cheng Kung University, Tainan 701, TaiwanThe BH3-only molecule Bad regulates cell death via its differential protein phosphorylation, but very few studies address its effect on early embryonic development in vertebrate systems. In this work, we examined the novel role of zebrafish Bad in the initial programmed cell death (PCD) for brain morphogenesis through reducing environmental stress and cell death signaling. Bad was considered to be a material factor that because of the knockdown of Bad by morpholino oligonucleotides, PCD was increased and the reactive oxygen species (ROS) level was enhanced, which correlated to trigger a p53/caspase-8 involving cell death signaling. This Bad knockdown-mediated environmental stress and enhanced cell dying can delay normal cell migration in the formation of the three germ layers, especially the ectoderm, for further brain development. Furthermore, Bad defects involved in three-germ-layers development at 8 hpf were identified by in situ hybridization approach on <i>cyp26</i>, <i>rtla</i>, and <i>Sox17</i> pattern expression markers. Finally, the Bad knockdown-induced severely defected brain was examined by tissue section from 24 to 48 h postfertilization (hpf), which correlated to induce dramatic malformation in the hindbrain. Our data suggest that the BH3-only molecule Bad regulates brain development via controlling programmed cell death on overcoming environmental stress for reducing secondary cell death signaling, which suggests that correlates to brain developmental and neurological disorders in this model system.https://www.mdpi.com/1422-0067/22/9/4832badbrain defectenvironmental stressp53/caspase-8 death signalinggene knockdown |
| spellingShingle | Jo-Chi Hung Jen-Leih Wu Jiann-Ruey Hong Proapoptotic <i>Bad</i> Involved in Brain Development, When Severely Defected, Induces Dramatic Malformation in Zebrafish International Journal of Molecular Sciences bad brain defect environmental stress p53/caspase-8 death signaling gene knockdown |
| title | Proapoptotic <i>Bad</i> Involved in Brain Development, When Severely Defected, Induces Dramatic Malformation in Zebrafish |
| title_full | Proapoptotic <i>Bad</i> Involved in Brain Development, When Severely Defected, Induces Dramatic Malformation in Zebrafish |
| title_fullStr | Proapoptotic <i>Bad</i> Involved in Brain Development, When Severely Defected, Induces Dramatic Malformation in Zebrafish |
| title_full_unstemmed | Proapoptotic <i>Bad</i> Involved in Brain Development, When Severely Defected, Induces Dramatic Malformation in Zebrafish |
| title_short | Proapoptotic <i>Bad</i> Involved in Brain Development, When Severely Defected, Induces Dramatic Malformation in Zebrafish |
| title_sort | proapoptotic i bad i involved in brain development when severely defected induces dramatic malformation in zebrafish |
| topic | bad brain defect environmental stress p53/caspase-8 death signaling gene knockdown |
| url | https://www.mdpi.com/1422-0067/22/9/4832 |
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