Flatt, K. | bioRxiv Science

bioRxiv2025

Interplay Between Pulmonary Membrane Properties and Lung Disease: a Study of Seven Bottlenose Dolphins

Pneumonia is the leading cause of morbidity and mortality of bottlenose dolphins Tursiops truncatus. We investigate a series of rare and opportunistic samples of pulmonary surfactant membranes (PSMs) extracted from lungs of seven dolphins in the care of the U.S. Navy Marine Mammal Program. We found a striking correlation between PSM structure, lipidome, and mechanical properties with the severity of lung injury. Specifically, lipidomics reveals exacerbated contents of cardiolipins, confirming a result obtained for terrestrial mammals afflicted by experimental pneumonia. Employing a battery of X-ray scattering, atomic force, and electron microscopy, we evaluate how the altered lipid composition impairs the structural integrity of the PSM and leads to dehydration and enhanced rigidity. Our findings demonstrate that the function of pulmonary surfactant membranes goes far beyond lowering alveolar surface tension, regulating their biochemical and biophysical properties with lung pathology progression. This knowledge will be useful to the development of future diagnostics and therapeutics of respiratory diseases targeting lung membranes.

biophysics↗

bioRxiv2018

The nidogen-domain containing protein DEX-1 is required for epidermal remodeling in C. elegans dauers

Phenotypic plasticity is a critical component of an organisms ability to thrive in an ever-changing environment. The free-living nematode, Caenorhabditis elegans, adapts to unfavorable environmental conditions by pausing reproductive development and entering a stress-resistant larval stage known as dauer. The transition into dauer is marked by vast morphological changes - including remodeling of epidermis, neurons and muscle. Though many of these dauer-specific traits have been described, the molecular basis of dauer-specific remodeling is still poorly understood. Here we show that the nidogen-domain containing protein DEX-1 functions downstream of the dauer decision to facilitate stage-specific tissue remodeling during dauer morphogenesis. DEX-1 was previously shown to regulate sensory dendrite formation during embryogenesis. We find that DEX-1 is also required for the proper remodeling of the stem cell-like epidermal seam cells and maintenance of seam cell quiescence during dauer. dex-1 mutant dauers lack distinct lateral cuticular alae during dauer and have increased sensitivity to sodium dodecyl sulfate (SDS). Furthermore, we find that DEX-1 mediated seam cell remodeling is required for proper dauer mobility. We show that DEX-1 acts cell autonomously in the seam cells during dauer and that dex-1 expression during dauer is regulated through DAF-16/FOXO-mediated derepression. Finally, we show that dex-1 interacts with a family of zona pellucida-domain encoding genes to regulate dauer-specific epidermal remodeling. Taken together, our data indicates that DEX-1 plays a central role in C. elegans epidermal remodeling during dauer.

genetics↗