PDGF signaling is required for primitive endoderm cell survival in the inner cell mass of the mouse blastocyst

Authors

  • Jérôme Artus,

    Corresponding author
    1. Developmental Biology Program, Sloan-Kettering Institute, New York, New York, USA
    2. Institut Pasteur, CNRS URA 2578, Mouse Functional Genetics, Paris, France
    • Correspondence: Jérôme Artus, Ph.D., Institut Pasteur, CNRS URA2578, Mouse Functional Genetics, 25 rue du docteur Roux, F-75015 Paris, France. Telephone: 33-1-4568–8486; Fax: 33-1-4568–8634; e-mail: jartus@pasteur.fr, web site: http://stemcells.free.fr; Anna-Katerina Hadjantonakis, Ph.D., Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, Box 371, New York, New York 10065, USA. Telephone: 1–212-639–8215; Fax: 1–646-422–2355; e-mail: hadj@mskcc.org, web site: http://www.mskcc.org/research/lab/anna-katerina-hadjantonakis

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  • Minjung Kang,

    1. Developmental Biology Program, Sloan-Kettering Institute, New York, New York, USA
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  • Michel Cohen-Tannoudji,

    1. Institut Pasteur, CNRS URA 2578, Mouse Functional Genetics, Paris, France
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  • Anna-Katerina Hadjantonakis

    Corresponding author
    1. Developmental Biology Program, Sloan-Kettering Institute, New York, New York, USA
    • Correspondence: Jérôme Artus, Ph.D., Institut Pasteur, CNRS URA2578, Mouse Functional Genetics, 25 rue du docteur Roux, F-75015 Paris, France. Telephone: 33-1-4568–8486; Fax: 33-1-4568–8634; e-mail: jartus@pasteur.fr, web site: http://stemcells.free.fr; Anna-Katerina Hadjantonakis, Ph.D., Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, Box 371, New York, New York 10065, USA. Telephone: 1–212-639–8215; Fax: 1–646-422–2355; e-mail: hadj@mskcc.org, web site: http://www.mskcc.org/research/lab/anna-katerina-hadjantonakis

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  • Author contribution: J.A.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of the manuscript; M.K.: collection and assembly of data, final approval of the manuscript; M.C.-T.: financial support, data analysis and interpretation, manuscript writing, final approval of the manuscript; A.-K.H.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of the manuscript.

Abstract

At the end of the preimplantation period, the inner cell mass (ICM) of the mouse blastocyst is composed of two distinct cell lineages, the pluripotent epiblast (EPI) and the primitive endoderm (PrE). The current model for their formation involves initial co-expression of lineage-specific markers followed by mutual-exclusive expression resulting in a salt-and-pepper distribution of lineage precursors within the ICM. Subsequent to lineage commitment, cell rearrangements and selective apoptosis are thought to be key processes driving and refining the emergence of two spatially distinct compartments. Here, we have addressed a role for Platelet Derived Growth Factor (PDGF) signaling in the regulation of programmed cell death during early mouse embryonic development. By combining genetic and pharmacological approaches, we demonstrate that embryos lacking PDGF activity exhibited caspase-dependent selective apoptosis of PrE cells. Modulating PDGF activity did not affect lineage commitment or cell sorting, suggesting that PDGF is involved in the fine-tuning of patterning information. Our results also indicate that PDGF and fibroblast growth factor (FGF) tyrosine kinase receptors exert distinct and non-overlapping functions in PrE formation. Taken together, these data uncover an early role of PDGF signaling in PrE cell survival at the time when PrE and EPI cells are segregated. Stem Cells 2013;31:1932-1941

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