title: miR-200c regulates FGFR-dependent epithelial proliferation via Vldlr during submandibular gland branching morphogenesis.
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.
authors: Matrix and Morphogenesis Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Ivan T
authors: IT
authors: Rebustini
authors: Toru
authors: T
authors: Hayashi
authors: Andrew D
authors: AD
authors: Reynolds
authors: Melvin L
authors: ML
authors: Dillard
authors: Ellen M
authors: EM
authors: Carpenter
authors: Matthew P
authors: MP
authors: Hoffman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D019295:Computational Biology; D004847:Epithelial Cells / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009024:Morphogenesis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D000091042:Reelin Protein; D013363:Submandibular Gland / Q000196:embryology*; D014162:Transfection
chemical_list: D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D011973:Receptors, LDL; D000091042:Reelin Protein; C036053:VLDL receptor; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; C000717128:Reln protein, mouse