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A feedback regulatory loop involving p53/miR-200 and growth hormone endocrine axis controls embryo size of zebrafish
In vertebrates, growth hormone/insulin-like growth factor (GH/IGF) axis signaling plays a critical role in regulating somatic growth. Understanding the direct upstream regulators of GH/IGF axis remains a major challenge. Our studies of the zebrafish reveal that the conserved miR-200 family members a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623745/ https://www.ncbi.nlm.nih.gov/pubmed/26507500 http://dx.doi.org/10.1038/srep15906 |
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author | Jing, Jing Xiong, Shuting Li, Zhi Wu, Junjie Zhou, Li Gui, Jian-Fang Mei, Jie |
author_facet | Jing, Jing Xiong, Shuting Li, Zhi Wu, Junjie Zhou, Li Gui, Jian-Fang Mei, Jie |
author_sort | Jing, Jing |
collection | PubMed |
description | In vertebrates, growth hormone/insulin-like growth factor (GH/IGF) axis signaling plays a critical role in regulating somatic growth. Understanding the direct upstream regulators of GH/IGF axis remains a major challenge. Our studies of the zebrafish reveal that the conserved miR-200 family members are critical regulators of embryo size by targeting several GH/IGF axis genes, including GH, GHRa, GHRb and IGF2a. Overexpression of miR-200s led to cell cycle arrest in the G1 phase and induced apoptotic responses during embryo development, thereby inhibiting somatic growth of zebrafish embryos. Intriguingly, GH induced expression of both p53 and miR-200s, and miR-200s is a potential p53 transcriptional target, thus forming a negative feedback loop. Significantly, the up-regulation of miR-200s associated with GH activation is abolished in embryos with p53 mutation. By integrating these studies, we conclude that p53/miR-200 and GH/IGF signaling pathway form a negative regulatory loop to control embryo size, that provide critical insights into the long-standing puzzle of how body growth is determined during early development of teleosts. |
format | Online Article Text |
id | pubmed-4623745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46237452015-11-03 A feedback regulatory loop involving p53/miR-200 and growth hormone endocrine axis controls embryo size of zebrafish Jing, Jing Xiong, Shuting Li, Zhi Wu, Junjie Zhou, Li Gui, Jian-Fang Mei, Jie Sci Rep Article In vertebrates, growth hormone/insulin-like growth factor (GH/IGF) axis signaling plays a critical role in regulating somatic growth. Understanding the direct upstream regulators of GH/IGF axis remains a major challenge. Our studies of the zebrafish reveal that the conserved miR-200 family members are critical regulators of embryo size by targeting several GH/IGF axis genes, including GH, GHRa, GHRb and IGF2a. Overexpression of miR-200s led to cell cycle arrest in the G1 phase and induced apoptotic responses during embryo development, thereby inhibiting somatic growth of zebrafish embryos. Intriguingly, GH induced expression of both p53 and miR-200s, and miR-200s is a potential p53 transcriptional target, thus forming a negative feedback loop. Significantly, the up-regulation of miR-200s associated with GH activation is abolished in embryos with p53 mutation. By integrating these studies, we conclude that p53/miR-200 and GH/IGF signaling pathway form a negative regulatory loop to control embryo size, that provide critical insights into the long-standing puzzle of how body growth is determined during early development of teleosts. Nature Publishing Group 2015-10-28 /pmc/articles/PMC4623745/ /pubmed/26507500 http://dx.doi.org/10.1038/srep15906 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Jing, Jing Xiong, Shuting Li, Zhi Wu, Junjie Zhou, Li Gui, Jian-Fang Mei, Jie A feedback regulatory loop involving p53/miR-200 and growth hormone endocrine axis controls embryo size of zebrafish |
title | A feedback regulatory loop involving p53/miR-200 and growth hormone endocrine axis controls embryo size of zebrafish |
title_full | A feedback regulatory loop involving p53/miR-200 and growth hormone endocrine axis controls embryo size of zebrafish |
title_fullStr | A feedback regulatory loop involving p53/miR-200 and growth hormone endocrine axis controls embryo size of zebrafish |
title_full_unstemmed | A feedback regulatory loop involving p53/miR-200 and growth hormone endocrine axis controls embryo size of zebrafish |
title_short | A feedback regulatory loop involving p53/miR-200 and growth hormone endocrine axis controls embryo size of zebrafish |
title_sort | feedback regulatory loop involving p53/mir-200 and growth hormone endocrine axis controls embryo size of zebrafish |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623745/ https://www.ncbi.nlm.nih.gov/pubmed/26507500 http://dx.doi.org/10.1038/srep15906 |
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