Exosomal MicroRNA Transport from Salivary Mesenchyme Regulates Epithelial Progenitor Expansion during Organogenesis

Publication date: Available online 29 December 2016
Source:Developmental Cell
Author(s): Toru Hayashi, Isabelle M.A. Lombaert, Belinda R. Hauser, Vaishali N. Patel, Matthew P. Hoffman
Epithelial-mesenchymal interactions involve fundamental communication between tissues during organogenesis and are primarily regulated by growth factors and extracellular matrix. It is unclear whether RNA-containing exosomes are mobile genetic signals regulating epithelial-mesenchymal interactions. Here we identify that exosomes loaded with mesenchyme-specific mature microRNA contribute mobile genetic signals from mesenchyme to epithelium. The mature mesenchymal miR-133b-3p, loaded into exosomes, was transported from mesenchyme to the salivary epithelium, which did not express primary miR-133b-3p. Knockdown of miR-133b-3p in culture decreased endbud morphogenesis, reduced proliferation of epithelial KIT⁺ progenitors, and increased expression of a target gene, Disco-interacting protein 2 homolog B (Dip2b). DIP2B, which is involved in DNA methylation, was localized with 5-methylcytosine in the prophase nucleus of a subset of KIT⁺ progenitors during mitosis. In summary, exosomal transport of miR-133b-3p from mesenchyme to epithelium decreases DIP2B, which may function as an epigenetic regulator of genes responsible for KIT⁺ progenitor expansion during organogenesis.

Graphical abstract

Teaser

Epithelial-mesenchymal interactions are critical for salivary gland development. Hayashi et al. show that miRNA-containing exosomes produced by mesenchyme are transported to the epithelium, where they regulate KIT⁺ progenitor cell proliferation. A specific mesenchymal miRNA (miR-133b-3p) targets DIP2B, which is involved in DNA methylation, thus regulating progenitor cell expansion during organogenesis.


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