Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development

Research output: Contribution to journalArticle

Authors

  • LA Van Meeteren
  • P Ruurs
  • C Stortelers
  • P Bouwman
  • MA van Rooljen
  • JP Pradere
  • JS Sulnier-Blache
  • CL Mummery
  • WH Moolenaar
  • J Jonkers

Colleges, School and Institutes

Abstract

Autotaxin (ATX), or nucleotide pyrophosphatase-phosphodiesterase 2, is a secreted lysophospholipase D that promotes cell migration, metastasis, and angiogenesis. ATX generates lysophosphatidic acid (LPA), a lipid mitogen and motility factor that acts on several G protein-coupled receptors. Here we report that ATX-deficient mice die at embryonic day 9.5 (E9.5) with profound vascular defects in yolk sac and embryo resembling the G alpha(13) knockout phenotype. Furthermore, at E8.5, ATX-deficient embryos showed allantois malformation, neural tube defects, and asymmetric headfolds. The onset of these abnormalities coincided with increased expression of ATX and LPA receptors in normal embryos. ATX heterozygous mice appear healthy but show half-normal ATX activity and plasma LPA levels. Our results reveal a critical role for ATX in vascular development, indicate that ATX is the major LPA-producing enzyme in vivo, and suggest that the vascular defects in ATX-deficient embryos may be explained by loss of LPA signaling through G alpha(13).

Details

Original languageEnglish
Pages (from-to)5015-5022
Number of pages8
JournalMolecular and Cellular Biology
Volume26
Publication statusPublished - 1 Jul 2006