title: Ectopic expression of Fgf3 leads to aberrant lineage segregation in the mouse parthenote preimplantation embryos.
abstract: BACKGROUND
  Parthenogenetic mammalian embryos were reported to die in utero no later than the 25-somite stage due to abnormal development of both embryonic and extraembryonic lineages. Interestingly, it has been shown that parthenogenetic ICM cells tend to differentiate more into primitive endoderm cells and less into epiblast and ES cells. Hence we are interested in studying the molecular mechanisms underlying lineage defects of parthenotes.
  
  
  RESULTS
  We found that parthenote inner cell masses (ICMs) contained decreased numbers of Sox2(+) /Nanog(+) epiblast cells but increased numbers of Gata4(+) primitive endoderm cells, indicating an unusual lineage segregation. We demonstrate for the first time that the increased Gata4 level in parthenotes may be explained by the strong up-regulation of Fgf3 and Fgfr2 phosphorylation. Inhibition of Fgfr2 activation by SU5402 in parthenotes restored normal Nanog and Gata4 levels without affecting Fgf3, indicating that Fgf3 is upstream of Fgfr2 activation. In parthenote trophectoderm, we detected normal Cdx2 but ectopic Gata4 expression and reduced Elf5 and Tbr2(Eomes) levels.
  
  
  CONCLUSIONS
  Taken together, our work provides for the first time the insight into the molecular mechanisms of the developmental defects of parthenogenetic embryos in both the trophectoderm and ICM.
authors.affiliation: Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004707:Endoderm / Q000378:metabolism; D005260:Female; D051518:Fibroblast Growth Factor 3 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D005855:Germ Layers / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D018613:Microscopy, Confocal; D010312:Parthenogenesis / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C500759:Elf5 protein, mouse; C491198:Eomes protein, mouse; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D020825:T-Box Domain Proteins; D014157:Transcription Factors; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2