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

Abstract

Salamanders possess a pair of lungs for active air breathing, but the lung respiration is fully operational only during the late stage of development, particularly after metamorphosis. Larval salamanders mainly exchange air through the gills and skin, thus sparing the developing lungs. Salamanders can repair their lungs after injury, but a comparative analysis of regenerative responses between the lungs of young and adult animals is lacking. In this study, lung resections were performed in both larval and adult newts (Pleurodeles waltl). The cellular dynamics, tissue morphology and organ function during lung regeneration were examined and the Yap mutants were produced with CRISPR tools. We found that salamander switches the regenerative strategies from morphological replication through the blastema formation to compensatory growth via resident epithelial cells proliferation upon pulmonary resection injury as it transitions beyond metamorphosis. The larval animals achieve lung regeneration by forming a transient blastema‐like structure and regrowing full‐sized developing lungs, albeit unventilated. The adults repair injured lungs via massive proliferating epithelial cells and by expanding the existing alveolar epithelium without neo‐alveolarization. Yap signalling promotes epithelial cell proliferation and prevents epithelial‐to‐mesenchymal transition to restore functional respiration. The salamanders have evolved distinct regenerative strategies for lung repair during different phases of life. Our results demonstrate a novel strategy for functional lung recovery by inducing epithelial cell proliferation to strengthen the remaining alveoli without rebuilding new alveoli.

The Synchronized Progression from Mitosis to Meiosis in Female Primordial Germ Cells between Layers and Broilers

“…After that, cells were incubated with anti-DDX4 (Abcam, Cambridge, UK, ab13840) in the blocking solution at 4 °C overnight and then with Alexa Fluor 488-conjugated donkey anti-rabbit IgG (Invitrogen, Waltham, MA, USA, A-21206) at room temperature for 60 min. After washing with PBS, cells were incubated with EdU staining buffer (1 mM CuSO4, 100 mM Tris, 100 mM ascorbic acid, and 10 mM fluorescent azide) for 30 min according to previous protocols [ 22 ]. Counterstaining of the nucleus was performed using DAPI (Solarbio, Beijing, China, C0060).…”

Salamanders aid research into mechanisms of non‐canonical organ regeneration for clinical applications

“…The lung of the salamander is a sac-like structure consisting of parallel aligned alveoli similar to those in mammals, pneumocytes, goblet cells, ciliated cells, and neuroepithelial endocrine cells [14,[28][29][30]. Jensen et al found that PNX could effectively induce organ-wide proliferation to restore lung mass, and half of the EdU þ cells were SFC þ pneumocytes, which accounted for about 20% of all pneumocytes [29].…”

“…The lung of the salamander is a sac‐like structure consisting of parallel aligned alveoli similar to those in mammals, pneumocytes, goblet cells, ciliated cells, and neuroepithelial endocrine cells [14, 28–30]. Jensen et al.…”

“…A study from Yin showed another interesting phenomenon in newt lung regeneration [30]. Organ‐wide proliferation in axolotl could also be observed after PNX in larvae newts, with the difference that the proliferating cells appeared to aggregate near the injury and gave rise to blastema‐like structures, resulting in whole lung intact regeneration after 1 month.…”