Developmental switch from morphological replication to compensatory growth for salamander lung regeneration.

Area of Science:

• Regenerative Biology
• Developmental Biology
• Comparative Physiology

Background:

• Salamanders breathe with lungs post-metamorphosis, using gills and skin before then.
• Lung repair capacity exists, but age-related regenerative differences are unstudied.
• Understanding these differences can reveal novel strategies for lung repair.

Purpose of the Study:

• Compare lung regeneration strategies in larval and adult newts after injury.
• Investigate the role of Yap signalling in salamander lung repair.
• Identify mechanisms for functional lung recovery.

Main Methods:

• Performed lung resections in larval and adult newts (Pleurodeles waltl).
• Analyzed cellular dynamics, tissue morphology, and organ function during regeneration.
• Generated Yap mutants using CRISPR-Cas9 technology.

Main Results:

• Larval newts regenerated lungs via blastema formation, creating unventilated but full-sized organs.
• Adult newts repaired lungs through epithelial cell proliferation and alveolar expansion, without new alveoli.
• Yap signalling was found to promote epithelial proliferation and prevent adverse cell transitions, aiding functional repair.

Conclusions:

• Salamanders exhibit distinct, age-dependent lung regenerative strategies: blastema formation in larvae and compensatory growth in adults.
• Yap signalling is crucial for adult lung repair, promoting proliferation and maintaining epithelial integrity.
• This study reveals a novel approach to functional lung recovery by enhancing existing alveoli through epithelial proliferation.