Document Detail

Multi-cellular rosettes in the mouse visceral endoderm facilitate the ordered migration of anterior visceral endoderm cells.
MedLine Citation:
PMID:  22346733     Owner:  NLM     Status:  MEDLINE    
The visceral endoderm (VE) is a simple epithelium that forms the outer layer of the egg-cylinder stage mouse embryo. The anterior visceral endoderm (AVE), a specialised subset of VE cells, is responsible for specifying anterior pattern. AVE cells show a stereotypic migratory behaviour within the VE, which is responsible for correctly orientating the anterior-posterior axis. The epithelial integrity of the VE is maintained during the course of AVE migration, which takes place by intercalation of AVE and other VE cells. Though a continuous epithelial sheet, the VE is characterised by two regions of dramatically different behaviour, one showing robust cell movement and intercalation (in which the AVE migrates) and one that is static, with relatively little cell movement and mixing. Little is known about the cellular rearrangements that accommodate and influence the sustained directional movement of subsets of cells (such as the AVE) within epithelia like the VE. This study uses an interdisciplinary approach to further our understanding of cell movement in epithelia. Using both wild-type embryos as well as mutants in which AVE migration is abnormal or arrested, we show that AVE migration is specifically linked to changes in cell packing in the VE and an increase in multi-cellular rosette arrangements (five or more cells meeting at a point). To probe the role of rosettes during AVE migration, we develop a mathematical model of cell movement in the VE. To do this, we use a vertex-based model, implemented on an ellipsoidal surface to represent a realistic geometry for the mouse egg-cylinder. The potential for rosette formation is included, along with various junctional rearrangements. Simulations suggest that while rosettes are not essential for AVE migration, they are crucial for the orderliness of this migration observed in embryos. Our simulations are similar to results from transgenic embryos in which Planar Cell Polarity (PCP) signalling is disrupted. Such embryos have significantly reduced rosette numbers, altered epithelial packing, and show abnormalities in AVE migration. Our results show that the formation of multi-cellular rosettes in the mouse VE is dependent on normal PCP signalling. Taken together, our model and experimental observations suggest that rosettes in the VE epithelium do not form passively in response to AVE migration. Instead, they are a PCP-dependent arrangement of cells that acts to buffer the disequilibrium in cell packing generated in the VE by AVE migration, enabling AVE cells to migrate in an orderly manner.
Georgios Trichas; Aaron M Smith; Natalia White; Vivienne Wilkins; Tomoko Watanabe; Abigail Moore; Bradley Joyce; Jacintha Sugnaseelan; Tristan A Rodriguez; David Kay; Ruth E Baker; Philip K Maini; Shankar Srinivas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-07
Journal Detail:
Title:  PLoS biology     Volume:  10     ISSN:  1545-7885     ISO Abbreviation:  PLoS Biol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-06-06     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  101183755     Medline TA:  PLoS Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1001256     Citation Subset:  IM    
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MeSH Terms
Cell Movement*
Cell Polarity
Computer Simulation
Embryo Culture Techniques
Embryo, Mammalian / cytology
Endoderm / cytology*
Epithelial Cells / cytology,  physiology*
Mice, Inbred C57BL
Mice, Inbred CBA
Microscopy, Polarization
Models, Biological
Time-Lapse Imaging
Grant Support
074246/Z04/Z//Wellcome Trust; BB/F011512/1//Biotechnology and Biological Sciences Research Council; MC_U120081320//Medical Research Council

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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