The lipid phosphatase LPP3 regulates extra-embryonic vasculogenesis and axis patterning

Diana Escalante-Alcalde, Lidia Hernandez, Hervé Le Stunff, Ryu Maeda, Hyun Shik Lee, J. R. Gang-Cheng, Vicki A. Sciorra, Ira Daar, Sarah Spiegel, Andrew J. Morris, Colin L. Stewart

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

Abstract

Bioactive phospholipids, which include sphingosine-1-phosphate, lysophosphatidic acid, ceramide and their derivatives regulate a wide variety of cellular functions in culture such as proliferation, apoptosis and differentiation. The availability of these lipids and their products is regulated by the lipid phosphate phosphatases (LPPs). Here we show that mouse embryos deficient for LPP3 fail to form a chorio-allantoic placenta and yolk sac vasculature. A subset of embryos also show a shortening of the anterior-posterior axis and frequent duplication of axial structures that are strikingly similar to the phenotypes associated with axin deficiency, a critical regulator of Wnt signaling. Loss of LPP3 results in a marked increase in β-catenin-mediated TCF transcription, whereas elevated levels of LPP3 inhibit β-catenin-mediated TCF transcription. LPP3 also inhibits axis duplication and leads to mild ventralization in Xenopus embryo development. Although LPP3 null fibroblasts show altered levels of bioactive phospholipids, consistent with loss of LPP3 phosphatase activity, mutant forms of LPP3, specifically lacking phosphatase activity, were able to inhibit β-catenin-mediated TCF transcription and also suppress axis duplication, although not as effectively as intact LPP3. These results reveal that LPP3 is essential to formation of the chorio-allantoic placenta and extra-embryonic vasculature. LPP3 also mediates gastrulation and axis formation, probably by influencing the canonical Wnt signaling pathway. The exact biochemical roles of LPP3 phosphatase activity and its undefined effect on β-catenin-mediated TCF transcription remain to be determined.

Original languageEnglish
Pages (from-to)4623-4637
Number of pages15
JournalDevelopment (Cambridge)
Volume130
Issue number19
DOIs
StatePublished - Oct 2003

Keywords

  • Axis duplication
  • Lipid phosphate phosphatase
  • Vasculogenesis
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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