Yap and its subcellular localization have distinct compartment-specific roles in the developing lung

Area of Science:

• Developmental Biology
• Cell Biology
• Molecular Biology

Background:

• The Hippo-yes-associated protein (Yap) pathway's role in lung development is unclear.
• Conflicting data exists on Yap's subcellular localization and its significance in lung development.

Purpose of the Study:

• To elucidate the specific roles of Yap and its nucleocytoplasmic shuttling in developing lung airway and alveolar compartments.
• To resolve controversies regarding Yap's subcellular localization dynamics and significance.

Main Methods:

• Investigating Yap-deficient lung morphogenesis.
• Analyzing the effects of nuclear Yap activation on lung development.
• Assessing the necessity of Yap nucleocytoplasmic shuttling in epithelial progenitors.

Main Results:

• Aberrant lung morphogenesis in Yap-deficient lungs stems from disrupted distal epithelial progenitor development.
• Nuclear Yap activation can rescue abnormalities in developing lungs.
• Yap nucleocytoplasmic shuttling is largely dispensable for branching morphogenesis and sacculation in epithelial progenitors.
• Sustained nuclear Yap in airways disrupts proximal-distal identity and halts epithelial differentiation.

Conclusions:

• Hippo-Yap signaling is vital for prenatal lung development.
• Nuclear Yap activation is sufficient for rescuing lung developmental defects.
• Yap nucleocytoplasmic shuttling is not essential for lung branching and sacculation but impacts airway identity and differentiation.