ABSTRACT
The Alpine Prosanto Formation (Middle Triassic) cropping out in the Ducan region in eastern Switzerland has yielded a rich fish and reptile fauna. Here, we present new pachypleurosaur remains from the upper part of the formation (Early Ladinian), similar to the previously known pachypleurosaurs from the Middle Triassic UNESCO World Heritage Site of Monte San Giorgio in southern Switzerland/northern Italy. From these remains, a new pachypleurosaur species, Prosantosaurus scheffoldi nov. gen. et spec., is described on the basis of six fairly complete skeletons, one disarticulated specimen and an isolated skull. As is typical for pachypleurosaurs and most other Triassic marine reptiles, the new taxon is based to a large degree on a combination of characters (e.g., nasals articulating broadly with the anterior margins of the prefrontals and lacking posterior processes; postorbitals with rounded anterior processes that articulate with the postfrontals anterolaterally) rather than on many unambiguous autapomorphies, although a few of the latter were found including (1) a premaxilla which is excluded from entering both the external and internal nares and (2) a parietal, which is distinctly longer than wide and carrying distinct anterolaterally angled processes. Phylogenetic relationships of the new taxon are tested within European Pachypleurosauria, revealing that the new species is the sister taxon to a clade including Serpianosaurus, Proneusticosaurus, and the monophyletic Neusticosaurus spp. Mapping of palaeogeographic and stratigraphical distribution of valid European pachypleurosaurs shows that a formerly proposed scenario of migration of pachypleurosaurs from the eastern Palaeotethys during the Olenekian into the Germanic Basin and a subsequent diversification and invasion during the Anisian into the intraplatform basins of the South Alpine realm must be re-assessed. The exceptional preservation and preparation of the Ducan fossils further allow the description of tooth replacement patterns for the first time in a European pachypleurosaur species. The "alveolarization" of replacement teeth, the horizontal replacement pattern, and the subsequent remodelling of the functional alveoli during tooth replacement supports the monophyly of Sauropterygia as discussed before. Supplementary Information: The online version contains supplementary material available at 10.1186/s13358-022-00254-2.
ABSTRACT
Uromodulin, the most abundant protein in normal urine, is essentially produced by the cells lining the thick ascending limb. There it regulates the activity of the cotransporter NKCC2 and is involved in sodium chloride handling and blood pressure regulation. Conflicting reports suggested that uromodulin may also be expressed in the distal convoluted tubule (DCT) where its role remains unknown. Using microdissection studies combined with fluorescent in situ hybridization and co-immunostaining analyses, we found a significant expression of uromodulin in mouse and human DCT at approximately 10% of thick ascending limb expression levels, but restricted to the early part of the DCT (DCT1). Genetic deletion of Umod in mouse was reflected by a major shift in NCC activity from the DCT1 to the downstream DCT2 segment, paralleled by a compensatory expansion of DCT2. By increasing the distal sodium chloride and calcium ion load with chronic furosemide administration, an intrinsic compensatory defect in the DCT from Umod-/- compared to wild type mice was found manifested as sodium wasting and hypercalciuria. In line, co-expression studies in HEK cells suggested a facilitating role for uromodulin in NCC phosphorylation, possibly via SPAK-OSR1 modulation. These experiments demonstrate a significant expression of uromodulin in the early part of mouse and human DCT. Thus, biosynthesis of uromodulin in the DCT1 is critical for its function, structure and plasticity, suggesting novel links between uromodulin, blood pressure control and risk of kidney stones.
