MicroRNA-92a Upholds Bmp Signaling by Targeting noggin3 during Pharyngeal Cartilage Formation

SummaryCraniofacial malformations are common structural birth defects and usually associate with abnormal development of pharyngeal arches. Although some microRNAs have been found to be implicated in chondrogenesis in vitro, few have been shown to be essential for cartilage and bone development at the whole organism level. In this study, we report that mir92a is highly enriched in the chondrogenic progenitors and that its inactivation results in loss of pharyngeal cartilage elements due to poor proliferation, impaired differentiation, and unsustainable survival of chondrogenic progenitors. The Bmp antagonist gene noggin3 (nog3) is a direct target of mir92a. Inactivation of mir92a stabilizes nog3 mRNA, leading to repression of Bmp signaling and abnormal behaviors of chondrogenic progenitors. In contrast, ectopic expression of mir92a duplex decreases nog3 mRNA levels and, as a result, derepresses Bmp signaling and promotes cell apoptosis. Therefore, mir92a acts to maintain Bmp activity during pharyngeal cartilage formation by targeting nog3.

Graphical AbstractFigure optionsDownload high-quality image (181 K)Download as PowerPoint slideHighlights
► mir92a inactivation leads to loss of pharyngeal cartilages in zebrafish embryos
► mir92a is required for chondrogenic progenitor proliferation and survival
► Bmp signaling is positively regulated by mir92a in the pharyngeal region
► nog3 mRNA is degraded by mir92a to maintain Bmp activity