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Journals The FASEB Journal Volume 22 Issue 10

LPA 1 is essential for lymphatic vessel development in zebrafish Shyh-Jye Lee * ,† ,1 , Tun-Hao Chan * ,2 , Tzu-Cheng Chen * ,2 , Bo-Kai Liao ‡ , Pung-Pung Hwang ‡ and Hsinyu Lee * ,† ,1 * Institute of Zoology and † Department of Life Science, National Taiwan University, Taipei, Taiwan; and ‡ Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan 1 Correspondence: 1 Roosevelt Rd., Section 4, Institute of Zoology, National Taiwan University, Taipei, Taiwan 106, R.O.C. E-mail: S.-J.L., jefflee@ntu.edu.tw ; H.L., hsinyulee@ntu.edu.tw Lysophosphatidic acid (LPA) has long been implicated in regulating vascular development via endothelial cell-expressed G protein-coupled receptors. However, because of a lack of notable vascular defects reported in LPA receptor knockout mouse studies, the regulation of vasculature by LPA receptors in vivo is still uncertain. Using zebrafish as a model, we studied the gene expression patterns and functions of an LPA receptor, LPA 1 , during embryonic development, in particular, vascular formation. Whole-mount in situ hybridization experiments revealed that zebrafish lpa 1 ( zlpa 1 ) was ubiquitously expressed early in development, and its expression domains were later localized to the head region and the vicinity of the dorsal aorta. The expression of zlpa 1 surrounding the dorsal aorta suggests its role in vasculature development. Knocking down of zLPA 1 by injecting morpholino (MO) oligonucleotides at 0.625–1.25 ng per embryo resulted in the absence of thoracic duct and edema in pericardial sac and trunk in a dose-dependent manner. These zlpa 1 -MO-resulted defects could be specifically rescued by ectopic expression of zlpa 1 . In addition, overexpression of vegf-c , a well-known lymphangiogenic factor, also partially ameliorated the inhibition of thoracic duct development. Taken together, these results demonstrate that LPA 1 is necessary for lymphatic vessel formation during embryonic development in zebrafish.—Lee, S.-J., Chan, T.-H., Chen, T.-C., Liao, B.-O., Hwang, P.-P., Lee, H. LPA 1 is essential for lymphatic vessel development in zebrafish. Key Words: lysophosphatidic acid • G protein-coupled receptor • endothelial cell • thoracic duct • morpholino

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LPA1 is essential for lymphatic vessel development in zebrafish

Lee, Shyh-Jye; Chan, Tun-Hao; Chen, Tzu-Cheng; Liao, Bo-Kai; Hwang, Pung-Pung; Lee, Hsinyu
The FASEB Journal , Volume 22 (10): 3706
Fed of American Socs for Experimental Biology – Oct 1, 2008

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