PUBLICATION

A feedback regulatory loop involving p53/miR-200 and growth hormone endocrine axis controls embryo size of zebrafish

Authors
Jing, J., Xiong, S., Li, Z., Wu, J., Zhou, L., Gui, J.F., Mei, J.
ID
ZDB-PUB-151029-4
Date
2015
Source
Scientific Reports   5: 15906 (Journal)
Registered Authors
Gui, Jian-Fang, Li, Zhi, Mei, Jie, Zhou, Li
Keywords
Gene regulation, miRNAs
MeSH Terms
  • Animals
  • Embryonic Development/genetics*
  • Feedback
  • Growth Hormone/genetics*
  • Insulin-Like Growth Factor I/genetics
  • MicroRNAs/genetics*
  • Signal Transduction/genetics
  • Tumor Suppressor Protein p53/genetics*
  • Up-Regulation/genetics
  • Zebrafish/embryology*
  • Zebrafish/genetics*
PubMed
26507500 Full text @ Sci. Rep.
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping