Hypoxia-inducible factor 1 alpha regulates the cardiac development through Autotaxin-Lpar3 signal pathway in zebrafish

• Main Authors: Wan-Ling Yao, 姚琬玲
• Other Authors: 李士傑
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/34116282395384644690

碩士 === 國立臺灣大學 === 動物學研究所 === 100 === Hypoxia is known to regulate gene expression via hypoxia- inducible factors (HIFs) and plays a role in many developmental processes, including vasculogenesis, angiogenesis, heart and central nervous system development. The Hif1α knockout mice shows defective heart development, including cardia bifida and abnormal neural crest migration. Recently, we have observed heart left-right asymmetric defects and cardia bifida in zebrafish embryos deficient in lysophosphatidic acid (LPA) synthesizing enzyme autotoxin and on of its receptors, LPAR3. LPA signaling stimulates cell proliferation, cell migration, survival of many cell types, tumorigenesis, angiogenesis, and metastasis. More interestingly, hypoxia is known to enhance LPA- induced Hif1α expression. Therefore, I hypothesize that Hif1α may regulate heart development through the Atx-Lpar3 pathway. Thus, I tested the idea that LPA may interact with HIF signaling to mediate cardiogenesis. Using the MO knockdown approach, I demonstrate that Hif1α and Lpar3 reciprocally regulate each other’s gene expression and rescues respective cardiac defects. Also, I investigate the connection between Hif1α and Atx. These results suggest that Hif1α, Atx and Lpar3 work together to mediate cardiac development.