期刊
DEVELOPMENTAL BIOLOGY
卷 344, 期 1, 页码 66-78出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2010.04.017
关键词
Cdx2; Trophectoderm; Mouse embryo; Polarisation; Cell death; Compaction
资金
- Wellcome Trust
- NIH [HD057970, HD01249]
- NICHD
- MRC [G0800784] Funding Source: UKRI
- Medical Research Council [G0800784, G0300723B, G0800784B] Funding Source: researchfish
Divisions of polarised blastomeres that allocate polar cells to outer and apolar cells to inner positions initiate the first cell fate decision in the mouse embryo. Subsequently, outer cells differentiate into trophectoderm while inner cells retain pluripotency to become inner cell mass (ICM) of the blastocyst Elimination of zygotic expression of trophectoderm-specific transcription factor Cdx2 leads to defects in the maintenance of the blastocyst cavity, suggesting that it participates only in the late stage of trophectoderm formation However, we now find that mouse embryos also have a maternally provided pool of Cdx2 mRNA. Moreover, depletion of both maternal and zygotic Cdx2 from immediately after fertilization by three independent approaches, dsRNAi siRNAi and morpholino oligonucleotides, leads to developmental arrest at much earlier stages than expected from elimination of only zygotic Cdx2 This developmental arrest is associated with defects in cell polarisation. reflected by expression and localisation of cell polarity molecules such as Par3 and aPKC and cell compaction at the 8- and 16-cell stages Cells deprived of Cdx2 show delayed development with increased cell cycle length, irregular cell division and increased incidence of apoptosis. Although some Cdx2-depleted embryos initiate cavitation, the cavity cannot be maintained Furthermore, expression of trophectoderm-specific genes. Gala3 and Comes, and also the trophectoderm-specific cytokeratin intermediate filament. recognised by Troma1, are greatly reduced or undetectable. Taken together, our results indicate that Cdx2 participates in two steps leading to trophectoderm specification appropriate polarisation of blastomeres at the 8- and 16-cell stage and then the maintenance of trophectoderm lineage-specific differentiation (C) 2010 Elsevier Inc All rights reserved
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