Maternally and zygotically provided Cdx2 have novel and critical roles for early development of the mouse embryo
| Autor: | Agnieszka Jedrusik, Magdalena Zernicka-Goetz, Maria Skamagki, Alexander W. Bruce, Meng How Tan, Denise E. Leong, Mylene W.M. Yao |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Cell death Cell division Cellular differentiation Compaction Apoptosis Cell fate determination Biology Models Biological Mouse embryo Article Mice 03 medical and health sciences 0302 clinical medicine Ectoderm Cell polarity medicine Animals Inner cell mass CDX2 Transcription Factor Blastocyst Molecular Biology In Situ Hybridization Fluorescence Protein Kinase C Polarisation reproductive and urinary physiology 030304 developmental biology Homeodomain Proteins 0303 health sciences 030219 obstetrics & reproductive medicine Gene Expression Regulation Developmental Cell Differentiation Embryo Cell Biology Immunohistochemistry Molecular biology Cell biology Mice Inbred C57BL medicine.anatomical_structure Cdx2 embryonic structures Maternal to zygotic transition Trophectoderm Female RNA Interference Transcription Factors Developmental Biology |
| Zdroj: | Developmental Biology |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2010.04.017 |
| Popis: | 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, Gata3 and Eomes, 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. |
| Databáze: | OpenAIRE |
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