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

摘要: In vertebrates, growth hormone/insulin-like factor (GH/IGF) axis signaling plays a critical role in regulating somatic growth. Understanding the direct upstream regulators of GH/IGF remains major challenge. Our studies zebrafish reveal that conserved miR-200 family members are embryo size by targeting several genes, including GH, GHRa, GHRb and IGF2a. Overexpression miR-200s led to cell cycle arrest G1 phase induced apoptotic responses during development, thereby inhibiting embryos. Intriguingly, GH expression both p53 miR-200s, is potential transcriptional target, thus forming negative feedback loop. Significantly, up-regulation associated with activation abolished embryos mutation. By integrating these studies, we conclude p53/miR-200 pathway form regulatory loop control size, provide insights into long-standing puzzle how body determined early development teleosts.