Document Detail


Maternally and zygotically provided Cdx2 have novel and critical roles for early development of the mouse embryo.
MedLine Citation:
PMID:  20430022     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Agnieszka Jedrusik; Alexander W Bruce; Meng H Tan; Denise E Leong; Maria Skamagki; Mylene Yao; Magdalena Zernicka-Goetz
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-27
Journal Detail:
Title:  Developmental biology     Volume:  344     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-23     Completed Date:  2010-08-10     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  66-78     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Cell Differentiation
Ectoderm / metabolism
Female
Gene Expression Regulation, Developmental*
Homeodomain Proteins / physiology*
Immunohistochemistry / methods
In Situ Hybridization, Fluorescence
Male
Mice
Mice, Inbred C57BL
Models, Biological
Protein Kinase C / metabolism
RNA Interference
Transcription Factors / physiology*
Grant Support
ID/Acronym/Agency:
064421//Wellcome Trust; G0800784//Medical Research Council; HD01249/HD/NICHD NIH HHS; HD057970/HD/NICHD NIH HHS; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Cdx2 protein, mouse; 0/Homeodomain Proteins; 0/Transcription Factors; EC 2.7.11.13/Protein Kinase C
Comments/Corrections

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