Mesenchymal miR-21 regulates branching morphogenesis in murine submandibular gland in vitro

Dev Biol. 2011 Apr 15;352(2):299-307. doi: 10.1016/j.ydbio.2011.01.030. Epub 2011 Feb 3.


Branching morphogenesis in murine submandibular glands (SMG) is regulated by growth factors, extracellular matrix (ECM) and many biological processes through interactions between the epithelium and the mesenchyme. MicroRNAs (miRNAs) are a set of small, non-protein-coding RNAs that regulate gene expression at the post-transcriptional level. We hypothesized that branching morphogenesis is partly regulated by miRNAs. Forty-four miRNAs and novel miRNA candidates were detected in SMG at embryonic day 13 by a cloning method combined with Argonaute-2 immunoprecipitation. MicroRNA21 (miR-21) expression in the mesenchyme was up-regulated and accelerated by epidermal growth factor, which is known to enhance branching morphogenesis in vitro. Down-regulation of miR-21 in the mesenchyme by locked nucleic acids was associated with a decrease in the number of epithelial buds. Relative quantification of candidates for target genes of miR-21 indicated that two messenger RNAs (for Reck and Pdcd4) were down-regulated in the mesenchyme, where miR-21 expression levels were up-regulated. These results suggest that branching morphogenesis is regulated by miR-21 through gene expression related to ECM degradation in the mesenchyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers / genetics
  • Down-Regulation
  • Epidermal Growth Factor / pharmacology
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation, Developmental
  • In Vitro Techniques
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Mice
  • Mice, Inbred ICR
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Morphogenesis
  • Nucleic Acid Conformation
  • Oligonucleotides / genetics
  • Sequence Homology, Nucleic Acid
  • Submandibular Gland / drug effects
  • Submandibular Gland / embryology*
  • Submandibular Gland / metabolism*
  • Transfection
  • Up-Regulation


  • DNA Primers
  • MIRN21 microRNA, mouse
  • MicroRNAs
  • Oligonucleotides
  • locked nucleic acid
  • Epidermal Growth Factor