The physiological functions of several organs rely on branched tubular networks, but little is known about conflicts in development between building enough tubules for adequate function and geometric constraints imposed by organ size. We show that the mouse embryonic kidney epithelium negotiates a physical packing conflict between tubule tip duplication and limited area at the organ surface. Imaging, computational, and soft material modeling of tubule ‘families’ identifies six geometric packing phases, including two defective ones. Experiments in kidney explants show that a retrograde tension on tubule families is necessary and sufficient for them to avoid defects by switching to a vertical orientation that increases packing density. These results reveal developmental contingencies in response to physical limitations, and create a framework for classifying kidney defects.One-Sentence SummaryEpithelial branching in the kidney causes a geometric packing conflict that is resolved through internally generated tensions
The kidney develops through elaboration of ureteric epithelial tubules (the future urinary collecting ducts), stroma, and nephron progenitors in the cap mesenchyme that surrounds each ureteric tip as they branch. Dynamic interactions between these tissues coordinate a balance between ureteric tip branching and nephron formation that sets nephron numbers for life, which impacts the probability of adult disease. How then is this balance achieved? Here we study the geometric and mechanical consequences of tubule tip crowding at the embryonic kidney surface and its effect on nephron formation. We find that kidney surface curvature reduces and tubule 'tip domains' pack more closely over developmental time. These together create a semi-crystalline geometry of tips at the kidney surface and a rigidity transition to more solid-like tissue properties at later developmental stages. New tips overcome mechanical resistance as they branch, expand, and displace close-packed neighbors, after which residual mechanical stress dissipates. This correlates with a changing nephrogenesis rate over the tip 'life-cycle'. To draw a causal link between the two, we mimic a mechanical transient in human iPSC-derived nephron progenitor organoids and find increased cell commitment to early nephron aggregates. The data suggest that temporal waves of mechanical stress within nephron progenitor populations could constitute a clock that synchronizes nephron formation and ureteric tubule duplication after E15. Ongoing efforts to understand the spatial and temporal regulation of nephron induction will clarify variation in nephron endowment between kidneys and advance engineered kidney tissues for regenerative medicine.
The title complex, [CuCl(2)(C(6)H(6)N(4)S(2))], has a flattened tetrahedral coordination. The Cu(II) atom is located on a twofold rotation axis and is coordinated by two N atoms from a chelating 2,2'-diamino-4,4'-bi-1,3-thiazole ligand and by two Cl atoms. Intramolecular hydrogen bonding exists between the amino groups of the 2,2'-diamino-4,4'-bi-1,3-thiazole ligand and the Cl atoms. The intermolecular separation of 3.425 (1) A between parallel bithiazole rings suggests there is a pi-pi interaction between them.
Key indicatorsSingle-crystal X-ray study T = 298 K Mean '(C±C) = 0.004 A Ê R factor = 0.050 wR factor = 0.137 Data-to-parameter ratio = 14.9For details of how these key indicators were automatically derived from the article, see
In the title compound, C7H7N2+·C8H4NO6−, the partially overlapped arrangement and the shorter face‐to‐face distance of 3.457 (4) Å indicate π–π stacking between parallel benzimidazolium cations, whereas the longer face‐to‐face distance of 3.649 (6) Å suggests normal van der Waals contacts between parallel benzene rings of neighbouring nitroterephthalate anions.
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