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Ectopic expression of Fgf3 leads to aberrant lineage segregation in the mouse parthenote preimplantation embryos
Author(s) -
Chen YiHui,
Yu John
Publication year - 2012
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.23851
Subject(s) - epiblast , biology , endoderm , embryo , homeobox protein nanog , blastocyst , inner cell mass , microbiology and biotechnology , sox2 , embryonic stem cell , genetics , embryogenesis , ectopic expression , gastrulation , andrology , cell culture , gene , medicine , induced pluripotent stem cell
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. Developmental Dynamics 241:1651–1664, 2012. © 2012 Wiley Periodicals,Inc.