What frog gill resorption brings: loss of function, cell death, and metabolic reorganization

Abstract

Abstract Background Anuran metamorphosis, driven by thyroid hormone-mediated processes, orchestrates intricate morphological and functional transformations for the transition from aquatic tadpoles to terrestrial life, providing a valuable model for studying organ functionalization, remodeling, and regression. Larva-specific organ regression is one of the most striking phenomena observed during anuran metamorphic climax. While previous studies extensively analyzed tail regression mechanisms, the molecular processes governing gill resorption remain elusive. Results We employ Microhyla fissipes as a mode, utilizing a comprehensive approach involving histological analysis, transmission electron microscopy, and transcriptomics to unravel the gill development and resorption. The pro-metamorphic stages reveal highly developed gill structures, emphasizing their crucial role as the primary respiratory organ for tadpoles. Transcriptomic analysis highlights the upregulation of genes associated with enhanced respiratory efficiency, such as hemoglobin and mucins. However, as metamorphosis progresses, gill filaments undergo shrinkage, blood vessel density decreases, and structural changes signify a decline in respiratory function. The molecular mechanisms driving gill resorption involve the thyroid hormone pathway, particularly the upregulation of thyroid hormone receptor β, genes associated with the tumor necrosis factor pathway and matrix metalloproteinases. Two distinct pathways orchestrate gill resorption, involving apoptosis directly induced by thyroid hormone and cell death through extracellular matrix degradation. In addition, metabolic reorganization during metamorphosis is a complex process, with tadpoles adapting their feeding behavior and mobilizing energy storage organs. The gills, previously overlooked, are unveiled as potential energy storage organs undergoing metabolic reorganization. Transcriptomic analysis reveals dynamic changes in metabolism-related genes, indicating decreased protein synthesis and energy production and enhanced substrate transport and metabolism during metamorphic climax. Conclusion This study sheds light on the structural, molecular, and metabolic dynamics during gill development and resorption in M. fissipes. The findings deepen our understanding of the intricate mechanisms governing organ regression and underscore the pivotal role of gill in facilitating the transition from aquatic to terrestrial habitats.