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Publication : TROP2 expressed in the trunk of the ureteric duct regulates branching morphogenesis during kidney development.

First Author  Tsukahara Y Year  2011
Journal  PLoS One Volume  6
Issue  12 Pages  e28607
PubMed ID  22194864 Mgi Jnum  J:182249
Mgi Id  MGI:5315060 Doi  10.1371/journal.pone.0028607
Citation  Tsukahara Y, et al. (2011) TROP2 expressed in the trunk of the ureteric duct regulates branching morphogenesis during kidney development. PLoS One 6(12):e28607
abstractText  TROP2, a cell surface protein structurally related to EpCAM, is expressed in various carcinomas, though its function remains largely unknown. We examined the expression of TROP2 and EpCAM in fetal mouse tissues, and found distinct patterns in the ureteric bud of the fetal kidney, which forms a tree-like structure. The tip cells in the ureteric bud proliferate to form branches, whereas the trunk cells differentiate to form a polarized ductal structure. EpCAM was expressed throughout the ureteric bud, whereas TROP2 expression was strongest at the trunk but diminished towards the tips, indicating the distinct cell populations in the ureteric bud. The cells highly expressing TROP2 (TROP2(high)) were negative for Ki67, a proliferating cell marker, and TROP2 and collagen-I were co-localized to the basal membrane of the trunk cells. TROP2(high) cells isolated from the fetal kidney failed to attach and spread on collagen-coated plates. Using MDCK cells, a well-established model for studying the branching morphogenesis of the ureteric bud, TROP2 was shown to inhibit cell spreading and motility on collagen-coated plates, and also branching in collagen-gel cultures, which mimic the ureteric bud's microenvironment. These results together suggest that TROP2 modulates the interaction between the cells and matrix and regulates the formation of the ureteric duct by suppressing branching from the trunk during kidney development.
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