A role for PDGF signaling in expansion of the extra-embryonic endoderm lineage of the mouse blastocyst Journal Article

   


Authors: Artus, J.; Panthier, J. J.; Hadjantonakis, A. K.
Article Title: A role for PDGF signaling in expansion of the extra-embryonic endoderm lineage of the mouse blastocyst
Abstract: The inner cell mass (ICM) of the implanting mammalian blastocyst comprises two lineages: the pluripotent epiblast (EPI) and primitive endoderm (PrE). We have identified platelet-derived growth factor receptor alpha (PDGFRα) as an early marker of the PrE lineage and its derivatives in both mouse embryos and ex vivo paradigms of extra-embryonic endoderm (ExEn). By combining live imaging of embryos and embryo-derived stem cells expressing a histone H2B-GFP fusion reporter under the control of Pdgfra regulatory elements with the analysis of lineage-specific markers, we found that Pdgfra expression coincides with that of GATA6, the earliest expressed transcriptional regulator of the PrE lineage. We show that GATA6 is required for the activation of Pdgfra expression. Using pharmacological inhibition and genetic inactivation we addressed the role of the PDGF pathway in the PrE lineage. Our results demonstrate that PDGF signaling is essential for the establishment, and plays a role in the proliferation, of XEN cells, which are isolated from mouse blastocyst stage embryos and represent the PrE lineage. Implanting Pdgfra mutant blastocysts exhibited a reduced number of PrE cells, an effect that was exacerbated by delaying implantation. Surprisingly, we also noted an increase in the number of EPI cells in implantation-delayed Pdgfra-null mutants. Taken together, our data suggest a role for PDGF signaling in the expansion of the ExEn lineage. Our observations also uncover a possible role for the PrE in regulating the size of the pluripotent EPI compartment.
Keywords: signal transduction; controlled study; nonhuman; cell proliferation; animal cell; mouse; mammalia; animals; mice; platelet derived growth factor alpha receptor; receptor, platelet-derived growth factor alpha; mitogen activated protein kinase kinase 1; mitogen activated protein kinase kinase 2; microscopy, confocal; embryo; embryonic stem cell; green fluorescent protein; cell lineage; gene activation; regulatory mechanism; reverse transcriptase polymerase chain reaction; promoter regions, genetic; tyrosine kinase receptor; green fluorescent proteins; cell count; protein kinase c; pluripotent stem cell; dna primers; ex vivo study; histone h2b; histones; endoderm; mutant; mouse embryo; blastocyst; epiblast; primitive endoderm; transcription factor gata 4; transcription factor gata 6; embryonic stem (es) cell; extra-embryonic endoderm; gata; pdgf signaling; xen cell; ectoderm; extraembryonic endoderm; receptor upregulation; blastocyst inner cell mass; extraembryonic membranes; gata6 transcription factor
Journal Title: Development
Volume: 137
Issue: 20
ISSN: 0950-1991
Publisher: Company of Biologists  
Date Published: 2010-10-15
Start Page: 3361
End Page: 3372
Language: English
DOI: 10.1242/dev.050864
PUBMED: 20826533
PROVIDER: scopus
PMCID: PMC2947752
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-77957680827&partnerID=40&md5=1dddfe343d34cdc9cb7ed4cef73e82eb
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "CODEN: DEVPE" - "Source: Scopus"
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MSK Authors
  1. Anna-Katerina Hadjantonakis
    193 Hadjantonakis
  2. Jerome Francois Artus
    15 Artus
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