| First Author | Koike S | Year | 2010 |
| Journal | Biochem Biophys Res Commun | Volume | 400 |
| Issue | 1 | Pages | 66-71 |
| PubMed ID | 20692235 | Mgi Jnum | J:164800 |
| Mgi Id | MGI:4835343 | Doi | 10.1016/j.bbrc.2010.08.008 |
| Citation | Koike S, et al. (2010) Deficiency of autotaxin/lysophospholipase D results in head cavity formation in mouse embryos through the LPA receptor-Rho-ROCK pathway. Biochem Biophys Res Commun 400(1):66-71 |
| abstractText | Autotaxin, encoded by the Enpp2 gene, generates lysophosphatidic acid (LPA) extracellularly, eliciting various cellular responses through specific LPA receptors. Previous studies have revealed that Enpp2(-/-) mice die at E9.5 owing to angiogenic defects in the yolk sac. Moreover, Enpp2(-/-) embryos show growth retardation, allantois malformation, no axial turning, and head cavity formation. We have also demonstrated that lysosome biogenesis is impaired in yolk sac visceral endoderm cells of Enpp2(-/-) embryos as a result of the downregulation of the Rho-ROCK (Rho-associated coiled-coil containing protein kinase)-LIM kinase pathway. In this study, we examine what signaling defect(s) is responsible for head cavity formation and yolk sac angiogenic defects. By using a whole embryo culture system, we show that 10 muM Ki16425, an antagonist for the LPA receptors, induces head cavity formation and yolk sac angiogenic defects in wild-type embryos. Moreover, 1 muM Ki16425 induces both phenotypes in Enpp2 heterozygous embryos at significantly higher incidence than in wild-type embryos, suggesting an interaction between autotaxin and LPA receptor signaling. Furthermore, we show that inhibition of the Rho-ROCK pathway induces head cavity formation, whereas multiple pathways are involved in yolk sac angiogenic defects. These results reveal the signal transduction defects that underlie the abnormalities in Enpp2(-/-) embryos. |
