Role of IGF signaling in catch-up growth and accelerated temporal development in zebrafish embryos in response to oxygen availability.
Animals respond to adverse environments by slowing down or arresting growth and development. Upon returning to normal conditions, they often show compensatory acceleration in growth and developmental rate. This phenomenon, known as `catch-up' growth, is widely documented in the animal kingdom. The underlying molecular mechanisms, however, are poorly understood. Using the zebrafish embryo as an experimental model system, we tested the hypothesis that changes in IGF signaling activities play an important role in the accelerated growth and temporal development resulting from re-oxygenation following hypoxia. We show that chronic hypoxia reduced, and re-oxygenation accelerated, embryonic growth and developmental rate. Whereas hypoxia repressed the Igf1 receptor and its downstream Erk1/2 and Akt signaling activities, re-oxygenation restored their activities. Specific inhibition of Igf1 receptor signaling during re-oxygenation by genetic and pharmacological approaches attenuated catch-up growth. Further analysis showed that whereas PI3K-Akt is required in both normal and catch-up growth, Mek1/2-Erk1/2 activation induced by elevated IGF signaling during re-oxygenation is particularly crucial for catch-up growth. These results suggest that the evolutionarily conserved IGF signaling pathway coordinates growth and temporal development in zebrafish embryos in response to oxygen availability.
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
Hiroyasu
H
Kamei
Yonghe
Y
Ding
Shingo
S
Kajimura
Michael
M
Wells
Peter
P
Chiang
Cunming
C
Duan
D000818:Animals; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D029961:Zebrafish Proteins; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010100:Oxygen