miR-200c regulates FGFR-dependent epithelial proliferation via Vldlr during submandibular gland branching morphogenesis.

TitlemiR-200c regulates FGFR-dependent epithelial proliferation via Vldlr during submandibular gland branching morphogenesis.
Publication TypeJournal Article
Year of Publication2012
AuthorsRebustini, IT, Hayashi T, Reynolds AD, Dillard ML, Carpenter EM, Hoffman MP
JournalDevelopment (Cambridge, England)
Volume139
Issue1
Pagination191-202
Date Published2012 Jan
ISSN1477-9129
KeywordsAnalysis 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
Abstract

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.

DOI10.1002/hbm.21441
Alternate JournalDevelopment