miR-200c regulates FGFR-dependent epithelial proliferation via Vldlr during submandibular gland branching morphogenesis.
|Title||miR-200c regulates FGFR-dependent epithelial proliferation via Vldlr during submandibular gland branching morphogenesis.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Rebustini, IT, Hayashi T, Reynolds AD, Dillard ML, Carpenter EM, Hoffman MP|
|Journal||Development (Cambridge, England)|
|Date Published||2012 Jan|
|Keywords||Analysis of Variance, Animals, Blotting, Western, Cell Proliferation, Computational Biology, Epithelial Cells, Fluorescent Antibody Technique, Gene Expression Regulation, Developmental, In Situ Hybridization, Mice, MicroRNAs, Morphogenesis, Real-Time Polymerase Chain Reaction, Receptor, Fibroblast Growth Factor, Type 1, Receptors, LDL, Submandibular Gland, Transfection|
The regulation of epithelial proliferation during organ morphogenesis is crucial for normal development, as dysregulation is associated with tumor formation. Non-coding microRNAs (miRNAs), such as miR-200c, are post-transcriptional regulators of genes involved in cancer. However, the role of miR-200c during normal development is unknown. We screened miRNAs expressed in the mouse developing submandibular gland (SMG) and found that miR-200c accumulates in the epithelial end buds. Using both loss- and gain-of-function, we demonstrated that miR-200c reduces epithelial proliferation during SMG morphogenesis. To identify the mechanism, we predicted miR-200c target genes and confirmed their expression during SMG development. We discovered that miR-200c targets the very low density lipoprotein receptor (Vldlr) and its ligand reelin, which unexpectedly regulate FGFR-dependent epithelial proliferation. Thus, we demonstrate that miR-200c influences FGFR-mediated epithelial proliferation during branching morphogenesis via a Vldlr-dependent mechanism. miR-200c and Vldlr may be novel targets for controlling epithelial morphogenesis during glandular repair or regeneration.