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 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.
College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Huazhong Agricultural University, Wuhan, 430070, China.
Jing
J
Jing
College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Huazhong Agricultural University, Wuhan, 430070, China.
Shuting
S
Xiong
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Wuhan 430072, China.
Zhi
Z
Li
College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Huazhong Agricultural University, Wuhan, 430070, China.
Junjie
J
Wu
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Wuhan 430072, China.
Li
L
Zhou
College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Huazhong Agricultural University, Wuhan, 430070, China.|State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Wuhan 430072, China.
Jian-Fang
JF
Gui
College of Fisheries, Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Huazhong Agricultural University, Wuhan, 430070, China.
Jie
J
Mei
D000818:Animals; D047108:Embryonic Development / Q000235:genetics*; D005246:Feedback; D013006:Growth Hormone / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*
D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone