Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

E-cadherin is required for intestinal morphogenesis in the mouse. Dev Biol 2012 Nov 01;371(1):1-12

Date

07/07/2012

Pubmed ID

22766025

Pubmed Central ID

PMC3455111

DOI

10.1016/j.ydbio.2012.06.005

Scopus ID

2-s2.0-84866479999   55 Citations

Abstract

E-cadherin, the primary epithelial adherens junction protein, has been implicated as playing a critical role in nucleating formation of adherens junctions, tight junctions, and desmosomes. In addition to its role in maintaining structural tissue integrity, E-cadherin has also been suggested as an important modulator of cell signaling via interactions with its cytoplasmic binding partners, catenins, as well as with growth factor receptors. Therefore, we proposed that loss of E-cadherin from the developing mouse intestinal epithelium would disrupt intestinal epithelial morphogenesis and function. To test this hypothesis, we used a conditional knockout approach to eliminate E-cadherin specifically in the intestinal epithelium during embryonic development. We found that E-cadherin conditional knockout mice failed to survive, dying within the first 24 hours of birth. Examination of intestinal architecture at E18.5 demonstrated severe disruption to intestinal morphogenesis in animals lacking E-cadherin in the epithelium of the small intestine. We observed changes in epithelial cell shape as well as in the morphology of villi. Although junctional complexes were evident, junctions were abnormal, and barrier function was compromised in E-cadherin mutant intestine. We also identified changes in the epithelial cell populations present in E-cadherin conditional knockout animals. The number of proliferating cells was increased, whereas the number of enterocytes was decreased. Although Wnt/β-catenin target mRNAs were more abundant in mutants compared with controls, the amount of nuclear activated β-catenin protein was dramatically lower in mutants compared with controls. In summary, our data demonstrate that E-cadherin is essential for intestinal epithelial morphogenesis and homeostasis during embryonic development.

Author List

Bondow BJ, Faber ML, Wojta KJ, Walker EM, Battle MA

Author

Michele A. Battle PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cadherins
Cell Adhesion
Fluorescent Antibody Technique
Homeostasis
Immunoblotting
Immunohistochemistry
Intestinal Mucosa
Intestine, Small
Mice
Mice, Knockout
Microscopy, Electron, Transmission
Morphogenesis
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
beta Catenin