PMID:22378759

Citation	Reardon, SN, King, ML, MacLean, JA 2nd, Mann, JL, DeMayo, FJ, Lydon, JP and Hayashi, K (2012) CDH1 is essential for endometrial differentiation, gland development, and adult function in the mouse uterus. Biol. Reprod. 86:141, 1-10
Abstract	CDH1 is a cell-cell adhesion molecule expressed in the epithelium to coordinate key morphogenetic processes, establish cell polarity, and regulate epithelial differentiation and proliferation. To determine the role of CDH1 in the mouse uterus, Cdh1 was conditionally ablated by crossing Pgr-Cre and Cdh1-flox mice, and the phenotype was characterized. We found that loss of Cdh1 results in a disorganized cellular structure of the epithelium and ablation of endometrial glands in the neonatal uterus. Cdh1(d/d) mice lost adherens junctions (CTNNB1 and CTNNA1) and tight junctions (claudin, occludin, and ZO-1 proteins) in the neonatal uterus, leading to loss of epithelial cell-cell interaction. Ablation of Cdh1 induced abnormal epithelial proliferation and massive apoptosis, and disrupted Wnt and Hox gene expression in the neonatal uterus. Although the uteri of Cdh1(d/d) mice did not show any myometrial defects, ablation of Cdh1 inhibited expression of epithelial (cytokeratin 8) and stromal (CD10) markers. Cdh1(d/d) mice were infertile because of defects during implantation and decidualization. Furthermore, we showed in the model of conditional ablation of both Cdh1 and Trp53 in the uterus that interrupting cell cycle regulation through the loss of Cdh1 leads to abnormal uterine development. The uteri of Cdh1(d/d) Trp53(d/d) mice exhibited histological features of endometrial carcinomas with myometrial invasion. Collectively, these findings suggest that CDH1 has an important role in structural and functional development of the uterus as well as adult uterine function. CDH1 has a capacity to control cell fate by altering directional cell proliferation and apoptosis.
Links	PubMed PMC3364924 Online version:10.1095/biolreprod.112.098871
Keywords	Adherens Junctions; Animals; Apoptosis/physiology; Carcinoma/genetics; Carcinoma/pathology; Carcinoma/physiopathology; Cell Cycle Proteins/genetics; Cell Cycle Proteins/physiology; Cell Differentiation/physiology; Cell Proliferation; Claudins/physiology; Endometrial Neoplasms/genetics; Endometrial Neoplasms/pathology; Endometrial Neoplasms/physiopathology; Endometrium/cytology; Endometrium/growth & development; Endometrium/physiology; Female; Gene Expression Regulation; Homeodomain Proteins/physiology; Keratin-8/biosynthesis; Membrane Proteins/physiology; Mice; Mice, Knockout; Neprilysin/biosynthesis; Phosphoproteins/physiology; Tight Junctions; Tumor Suppressor Protein p53/biosynthesis; Uterus/physiology; Wnt Signaling Pathway/physiology; alpha Catenin/physiology; beta Catenin/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:CADH1		GO:0035847: uterine epithelium development	ECO:0000315:		P		Fig. 1	complete CACAO 3920
MOUSE:CADH1		GO:0007566: embryo implantation	ECO:0000315:		P		Fig. 5	complete CACAO 3921
MOUSE:CADH1	involved_in	GO:0046697: decidualization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:CADH1		GO:0046697: decidualization	ECO:0000315:		P		Fig. 5c	complete CACAO 3922
MOUSE:CADH1	involved_in	GO:0007566: embryo implantation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:CADH1	involved_in	GO:0035847: uterine epithelium development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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