The Proapoptotic Gene <i>Bad</i> Regulates Brain Development via p53-Mediated Stress Signals in Zebrafish

Studies have shown that the BH3-only domain Bad regulates brain development via the control of programmed cell death (PCD), but very few studies have addressed its effect on the molecular signaling of brain development in the system. In this work, we examined the novel role of zebrafish <i>Bad...

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Autores principales:	Jo-Chi Hung, Jen-Leih Wu, Huei-Ching Li, Hsuan-Wen Chiu, Jiann-Ruey Hong
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	PCD <i>Bad</i> brain defect environmental stress p53/caspase-8 death signaling knockdown Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a35fee592a0c4b8e90b0b9b5745d24a2
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spelling	oai:doaj.org-article:a35fee592a0c4b8e90b0b9b5745d24a22021-11-25T17:07:34ZThe Proapoptotic Gene <i>Bad</i> Regulates Brain Development via p53-Mediated Stress Signals in Zebrafish10.3390/cells101128202073-4409https://doaj.org/article/a35fee592a0c4b8e90b0b9b5745d24a22021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2820https://doaj.org/toc/2073-4409Studies have shown that the BH3-only domain Bad regulates brain development via the control of programmed cell death (PCD), but very few studies have addressed its effect on the molecular signaling of brain development in the system. In this work, we examined the novel role of zebrafish <i>Bad</i> in initial programmed cell death for brain morphogenesis through the priming of p53-mediated stress signaling. In a biological function study on the knockdown of <i>Bad</i> by morpholino oligonucleotides, at 24 h post-fertilization (hpf) <i>Bad</i> defects induced abnormal hindbrain development, as determined in a tissue section by means of HE staining which traced the damaged hindbrain. Then, genome-wide approaches for monitoring either the upregulation of apoptotic-related genes (11.8%) or the downregulation of brain development-related genes (29%) at the 24 hpf stage were implemented. The p53/caspase-8-mediated apoptotic death pathway was strongly involved, with the pathway being strongly reversed in a <i>p53</i> mutant (<i>p53<sup>M214K</sup></i>) line during <i>Bad</i> knockdown. Furthermore, we propose the involvement of a p53-mediated stress signal which is correlated with regulating Bad loss-mediated brain defects. We found that some major genes in brain development, such as <i>crybb1</i>, <i>pva1b5</i>, <i>irx4a</i>, <i>pax7a</i>, and <i>fabp7a</i>, were dramatically restored in the <i>p53<sup>M214K</sup></i> line, and brain development recovered to return movement behavior to normal. Our findings suggest that Bad is required for (PCD) control, exerting a p53 stress signal on caspase-8/tBid-mediated death signaling and brain development-related gene regulation.Jo-Chi HungJen-Leih WuHuei-Ching LiHsuan-Wen ChiuJiann-Ruey HongMDPI AGarticlePCD<i>Bad</i>brain defectenvironmental stressp53/caspase-8 death signalingknockdownBiology (General)QH301-705.5ENCells, Vol 10, Iss 2820, p 2820 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	PCD <i>Bad</i> brain defect environmental stress p53/caspase-8 death signaling knockdown Biology (General) QH301-705.5
spellingShingle	PCD <i>Bad</i> brain defect environmental stress p53/caspase-8 death signaling knockdown Biology (General) QH301-705.5 Jo-Chi Hung Jen-Leih Wu Huei-Ching Li Hsuan-Wen Chiu Jiann-Ruey Hong The Proapoptotic Gene <i>Bad</i> Regulates Brain Development via p53-Mediated Stress Signals in Zebrafish
description	Studies have shown that the BH3-only domain Bad regulates brain development via the control of programmed cell death (PCD), but very few studies have addressed its effect on the molecular signaling of brain development in the system. In this work, we examined the novel role of zebrafish <i>Bad</i> in initial programmed cell death for brain morphogenesis through the priming of p53-mediated stress signaling. In a biological function study on the knockdown of <i>Bad</i> by morpholino oligonucleotides, at 24 h post-fertilization (hpf) <i>Bad</i> defects induced abnormal hindbrain development, as determined in a tissue section by means of HE staining which traced the damaged hindbrain. Then, genome-wide approaches for monitoring either the upregulation of apoptotic-related genes (11.8%) or the downregulation of brain development-related genes (29%) at the 24 hpf stage were implemented. The p53/caspase-8-mediated apoptotic death pathway was strongly involved, with the pathway being strongly reversed in a <i>p53</i> mutant (<i>p53<sup>M214K</sup></i>) line during <i>Bad</i> knockdown. Furthermore, we propose the involvement of a p53-mediated stress signal which is correlated with regulating Bad loss-mediated brain defects. We found that some major genes in brain development, such as <i>crybb1</i>, <i>pva1b5</i>, <i>irx4a</i>, <i>pax7a</i>, and <i>fabp7a</i>, were dramatically restored in the <i>p53<sup>M214K</sup></i> line, and brain development recovered to return movement behavior to normal. Our findings suggest that Bad is required for (PCD) control, exerting a p53 stress signal on caspase-8/tBid-mediated death signaling and brain development-related gene regulation.
format	article
author	Jo-Chi Hung Jen-Leih Wu Huei-Ching Li Hsuan-Wen Chiu Jiann-Ruey Hong
author_facet	Jo-Chi Hung Jen-Leih Wu Huei-Ching Li Hsuan-Wen Chiu Jiann-Ruey Hong
author_sort	Jo-Chi Hung
title	The Proapoptotic Gene <i>Bad</i> Regulates Brain Development via p53-Mediated Stress Signals in Zebrafish
title_short	The Proapoptotic Gene <i>Bad</i> Regulates Brain Development via p53-Mediated Stress Signals in Zebrafish
title_full	The Proapoptotic Gene <i>Bad</i> Regulates Brain Development via p53-Mediated Stress Signals in Zebrafish
title_fullStr	The Proapoptotic Gene <i>Bad</i> Regulates Brain Development via p53-Mediated Stress Signals in Zebrafish
title_full_unstemmed	The Proapoptotic Gene <i>Bad</i> Regulates Brain Development via p53-Mediated Stress Signals in Zebrafish
title_sort	proapoptotic gene <i>bad</i> regulates brain development via p53-mediated stress signals in zebrafish
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a35fee592a0c4b8e90b0b9b5745d24a2
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The Proapoptotic Gene <i>Bad</i> Regulates Brain Development via p53-Mediated Stress Signals in Zebrafish

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