Document Detail

Deficiency of autotaxin/lysophospholipase D results in head cavity formation in mouse embryos through the LPA receptor-Rho-ROCK pathway.
MedLine Citation:
PMID:  20692235     Owner:  NLM     Status:  MEDLINE    
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 μM Ki16425, an antagonist for the LPA receptors, induces head cavity formation and yolk sac angiogenic defects in wild-type embryos. Moreover, 1 μM 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.
Seiichi Koike; Kazuko Keino-Masu; Masayuki Masu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-06
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  400     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-13     Completed Date:  2010-10-11     Revised Date:  2011-11-07    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  66-71     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Department of Molecular Neurobiology, Graduate School of Comprehensive Human Sciences, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.
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MeSH Terms
Actins / metabolism
Blood Vessels / abnormalities
Embryo, Mammalian / abnormalities*,  metabolism
Head / abnormalities*
Mice, Mutant Strains
Multienzyme Complexes / genetics*
Neovascularization, Physiologic / genetics
Phosphodiesterase I / genetics*
Phosphoric Diester Hydrolases / genetics*
Pyrophosphatases / genetics*
Receptors, Lysophosphatidic Acid / antagonists & inhibitors,  metabolism*
Rho Factor / antagonists & inhibitors,  metabolism*
Signal Transduction / genetics
Yolk Sac / abnormalities,  blood supply
rho-Associated Kinases / antagonists & inhibitors,  metabolism*
Reg. No./Substance:
0/Actins; 0/Multienzyme Complexes; 0/Receptors, Lysophosphatidic Acid; 0/Rho Factor; EC Kinases; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC I; EC phosphodiesterase; EC 3.6.1.-/Pyrophosphatases

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