ATX expression and LPA signalling are vital for the development of the nervous system

Stella Fotopoulou, Nikos Oikonomou, Elena Grigorieva, Ioanna Nikitopoulou, Triantafillos Paparountas, Artemis Thanassopoulou, Zhenwen Zhao, Yan Xu, Dimitris L. Kontoyiannis, Eumorphia Remboutsika, Vassilis Aidinis

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Autotaxin (ATX) is a secreted glycoprotein widely present in biological fluids, originally isolated from the supernatant of melanoma cells as an autocrine motility stimulation factor. Its enzymatic product, lysophosphatidic acid (LPA), is a phospholipid mediator that evokes growth-factor-like responses in almost all cell types through G-protein coupled receptors. To assess the role of ATX and LPA signalling in pathophysiology, a conditional knockout mouse was created. Ubiquitous, obligatory deletion resulted to embryonic lethality most likely due to aberrant vascular branching morphogenesis and chorio-allantoic fusion. Moreover, the observed phenotype was shown to be entirely depended on embryonic, but not extraembryonic or maternal ATX expression. In addition, E9.5 ATX null mutants exhibited a failure of neural tube closure, most likely independent of the circulatory failure, which correlated with decreased cell proliferation and increased cell death. More importantly, neurite outgrowth in embryo explants was severely compromised in mutant embryos but could be rescued upon the addition of LPA, thus confirming a role for ATX and LPA signalling in the development of the nervous system. Finally, expression profiling of mutant embryos revealed attenuated embryonic expression of HIF-1a in the absence of ATX, suggesting a novel effector pathway of ATX/LPA.

Original languageEnglish (US)
Pages (from-to)451-464
Number of pages14
JournalDevelopmental Biology
Volume339
Issue number2
DOIs
StatePublished - Mar 15 2010

Keywords

  • Autotaxin (ATX)
  • Conditional knock out mouse
  • Hypoxia inducible factor 1a (HIF-1a)
  • Lysophosphatidic acid (LPA)
  • Neuronal development

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

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  • Cite this

    Fotopoulou, S., Oikonomou, N., Grigorieva, E., Nikitopoulou, I., Paparountas, T., Thanassopoulou, A., Zhao, Z., Xu, Y., Kontoyiannis, D. L., Remboutsika, E., & Aidinis, V. (2010). ATX expression and LPA signalling are vital for the development of the nervous system. Developmental Biology, 339(2), 451-464. https://doi.org/10.1016/j.ydbio.2010.01.007