miR-212 and miR-132 are required for epithelial stromal interactions necessary for mouse mammary gland development.
MicroRNAs are small noncoding RNAs that carry out post-transcriptional regulation of the expression of their target genes. However, their roles in mammalian organogenesis are only beginning to be understood. Here we show that the microRNA-212/132 family (which comprises miR-212 and miR-132) is indispensable during the development of the mammary glands in mice, particularly for the regulation of the outgrowth of the epithelial ducts. Mammary transplantation experiments revealed that the function of the miR-212/132 family is required in the stroma but not in the epithelia. Both miR-212 and miR-132 are expressed exclusively in mammary stroma and directly target the matrix metalloproteinase MMP-9. In glands that lack miR-212 and miR-132, MMP-9 expression increases and accumulates around the ducts. This may interfere with collagen deposition and lead to hyperactivation of the tumor growth factor-β signaling pathway, thereby impairing ductal outgrowth. Our results identify the miR-212/132 family as one of the main regulators of the epithelial-stromal interactions that are required for proper pubertal development of the mammary gland.
Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Goettingen, Germany.
Ahmet
A
Ucar
Vida
V
Vafaizadeh
Hubertus
H
Jarry
Jan
J
Fiedler
Petra A B
PA
Klemmt
Thomas
T
Thum
Bernd
B
Groner
Kamal
K
Chowdhury
D000818:Animals; D002450:Cell Communication; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D008321:Mammary Glands, Animal / Q000201:enzymology / Q000254:growth & development* / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
C546976:MIRN132 microRNA, mouse; C554518:MIRN212 microRNA, mouse; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D020780:Matrix Metalloproteinase 9