Catch-Up Growth in Zebrafish Embryo Requires Neural Crest Cells Sustained by Irs1 Signaling

• DOI: 10.1210/en.2017-00847
• Publication Date: 2018-01-30T14:07:04Z
• Authors: Hiroyasu Kamei; Yosuke Yoneyama; Fumihiko Hakuno; Rie Sawada; Toshiaki Shimizu; Cunming Duan; Shin-Ichiro Takah...
• Keywords: 0301 basic medicine; Embryo, Nonmammalian; Multipotent Stem Cells; Embryonic Development; 3. Good health; 03 medical and health sciences; Neural Crest; Insulin Receptor Substrate Proteins; Animals; Hypoxia; Proto-Oncogene Proteins c-akt; Zebrafish; Signal Transduction

Most animals display retarded growth in adverse conditions; however, upon the removal of unfavorable factors, they often show quick growth restoration, which is known as "catch-up" growth. In zebrafish embryos, hypoxia causes growth arrest, but subsequent reoxygenation induces catch-up growth. Here, we report the role of insulin receptor substrate (Irs)1-mediated insulin/insulinlike growth factor signaling (IIS) and the involvement of stem cells in catch-up growth in reoxygenated zebrafish embryos. Disturbed irs1 expression attenuated IIS, resulting in greater inhibition in catch-up growth than in normal growth and forced IIS activation‒restored catch-up growth. The irs1 knockdown induced noticeable cell death in neural crest cells (NCCs; multipotent stem cells) under hypoxia, and the pharmacological/genetic ablation of NCCs hindered catch-up growth. Furthermore, inhibition of the apoptotic pathway by pan-caspase inhibition or forced activation of Akt signaling in irs1 knocked-down embryos blocked NCC cell death and rescued catch-up growth. Our data indicate that this multipotent stem cell is indispensable for embryonic catch-up growth and that Irs1-mediated IIS is a prerequisite for its survival under severe adverse environments such as prolonged hypoxia.