The mesenchymal compartment of the lung plays a crucial role during lung development but, unlike its epithelial counterpart, its regulation is largely uncharacterised. Now, Gianni Carraro, Saverio Bellusci and colleagues report that miR-142-3p modulates WNT signalling to balance mesenchymal cell proliferation and differentiation during mouse lung development (). Using microarray analyses, the researchers identify miR-142-3p as highly expressed in the embryonic lung mesenchyme. Importantly, loss-of-function assays demonstrate that miR-142-3p regulates cell proliferation specifically in the mesenchyme; in the absence of miR-142-3p, progenitor cells prematurely differentiate. They also show that miR-142-3p binds to and regulates the expression of mRNA encoding APC, a negative regulator of WNT signalling. Accordingly, miR-142-3p knockdown can be rescued by activating WNT or reducing APC expression in the mesenchyme. Based on their findings, the authors propose that miR-142-3p adds an extra layer of control to the WNT-FGF feedback loop that operates in the lung mesenchyme to correctly balance cell proliferation and differentiation.
