Dynamic Hippo pathway activity underlies mesenchymal differentiation during lung alveolar morphogenesis

Area of Science:

• Developmental Biology
• Cell Biology
• Pulmonary Medicine

Background:

• Alveologenesis, the final stage of lung development, expands gas exchange surface area.
• Secondary crest myofibroblasts (SCMF) are transient cells critical for alveologenesis.
• Regulatory pathways governing SCMF function and identity are poorly understood.

Purpose of the Study:

• Investigate the role of Hippo signaling pathway components in alveologenesis.
• Determine the function of Yap/Taz effectors in SCMF during lung development.

Main Methods:

• Purification of SCMFs from reporter mice and bulk RNA-sequencing.
• Conditional deletion of Yap/Taz in Acta2-expressing cells.
• Single-cell RNA-sequencing and in vitro functional assays.

Main Results:

• Dynamic changes in Hippo-signaling components were observed during alveologenesis.
• Deletion of Yap/Taz arrested alveolar development and altered mesenchymal cell identity.
• Yap/Taz regulates myofibroblast gene expression and contractility in vitro.

Conclusions:

• Yap/Taz signaling is essential for maintaining the functional identity of myofibroblasts.
• This pathway is crucial for normal postnatal alveologenesis and lung development.