title: Autotaxin in embryonic development.
abstract: Autotaxin (ATX) is a secreted lysophospholipase D that generates the multifunctional lipid mediator lysophosphatidic acid (LPA). LPA signals through six distinct G protein-coupled receptors, acting alone or in concert to activate multiple effector pathways. The ATX-LPA signaling axis is implicated in a remarkably wide variety of physiological and pathological processes and plays a vital role in embryonic development. Disruption of the ATX-encoding gene (Enpp2) in mice results in intrauterine death due to vascular defects in the extra-embryonic yolk sac and embryo proper. In addition, Enpp2 (-/-) embryos show impaired neural development. The observed angiogenic defects are attributable, at least in part, to loss of LPA signaling through the Gα(12/13)-linked RhoA-ROCK-actin remodeling pathway. Studies in zebrafish also have uncovered a dual role for ATX in both vascular and neural development; furthermore, they point to a key role for ATX-LPA signaling in the regulation of left-right asymmetry. Here we discuss our present understanding of the role of ATX-LPA signaling in vertebrate development. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.
authors.affiliation: Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. w.moolenaar@nki.nl
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Moolenaar
authors.forename: Anna J S
authors.initials: AJ
authors.lastname: Houben
authors.forename: Shyh-Jye
authors.initials: SJ
authors.lastname: Lee
authors.forename: Laurens A
authors.initials: LA
authors.lastname: van Meeteren
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000378:metabolism; D019521:Body Patterning; D047108:Embryonic Development; D006801:Humans; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D000099189:Lysophospholipase D
chemical_list: D010727:Phosphoric Diester Hydrolases; D049368:Receptors, Lysophosphatidic Acid; D049349:Receptors, Lysosphingolipid; D000099189:Lysophospholipase D