LPA₁ is essential for lymphatic vessel development in zebrafish

• Published in: The FASEB journal 2008-10, Vol.22 (10), p.3706-3715
• Main Authors: Lee, Shyh-Jye, Chan, Tun-Hao, Chen, Tzu-Cheng, Liao, Bo-Kai, Hwang, Pung-Pung, Lee, Hsinyu
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Cloning, Molecular; Embryonic Development - genetics; endothelial cell; G protein‐coupled receptor; lysophosphatidic acid; Molecular Sequence Data; morpholino; Oligonucleotides, Antisense - genetics; Phylogeny; Receptors, Lysophosphatidic Acid - classification; Receptors, Lysophosphatidic Acid - genetics; Receptors, Lysophosphatidic Acid - physiology; RNA Splicing; Sequence Analysis, Protein; thoracic duct; Thoracic Duct - embryology; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins - classification; Zebrafish Proteins - genetics; Zebrafish Proteins - physiology
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.08-106088

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, LPA₁, during embryonic development, in particular, vascular formation. Whole-mount in situ hybridization experiments revealed that zebrafish lpa₁ (zlpa₁) 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 zlpa₁ surrounding the dorsal aorta suggests its role in vasculature development. Knocking down of zLPA₁ 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 zlpa₁-MO-resulted defects could be specifically rescued by ectopic expression of zlpa₁. 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 LPA₁ 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. LPA₁ is essential for lymphatic vessel development in zebrafish.