LPA1 is essential for lymphatic vessel development in zebrafish

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.