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ZFIN ID: ZDB-PUB-080825-27
K-ras/PI3K-Akt signaling is essential for zebrafish hematopoiesis and angiogenesis
Liu, L., Zhu, S., Gong, Z., and Low, B.C.
Date: 2008
Source: PLoS One   3(8): e2850 (Journal)
Registered Authors: Gong, Zhiyuan, Liu, Lihui, Zhu, Shizhen
Keywords: Embryos, Zebrafish, Ras signaling, Hematopoiesis, Red blood cells, Angiogenesis, Veins, Blood vessels
MeSH Terms:
  • Animals
  • Hematopoiesis/physiology*
  • Neovascularization, Physiologic/physiology*
  • Phosphatidylinositol 3-Kinases/physiology*
  • Proto-Oncogene Proteins c-akt/physiology*
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins/physiology*
  • ras Proteins/physiology*
PubMed: 18682746 Full text @ PLoS One
The RAS small GTPases orchestrate multiple cellular processes. Studies on knock-out mice showed the essential and sufficient role of K-RAS, but not N-RAS and H-RAS in embryonic development. However, many physiological functions of K-RAS in vivo remain unclear. Using wild-type and fli1:GFP transgenic zebrafish, we showed that K-ras-knockdown resulted in specific hematopoietic and angiogenic defects, including the impaired expression of erythroid-specific gene gata1 and sse3-hemoglobin, reduced blood circulation and disorganized blood vessels. Expression of either K-rasC40 that links to phosphoinositide 3-kinase (PI3K) activation, or Akt2 that acts downstream of PI3K, could rescue both hematopoietic and angiogenic defects in the K-ras knockdown. Consistently, the functional rescue by k-ras mRNA was significantly suppressed by wortmannin, a PI3K-specific inhibitor. Our results provide direct evidence that PI3K-Akt plays a crucial role in mediating K-ras signaling during hematopoiesis and angiogenesis in vivo, thus offering new targets and alternative vertebrate model for studying these processes and their related diseases.