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The developing murine kidney actively negotiates geometric packing conflicts to avoid defects

L. Prahl, John M. Viola, Jia‐Geng Liu, Alex J. Hughes

2023Developmental Cell16 citationsDOIOpen Access PDF

Abstract

The physiological functions of several organs rely on branched epithelial tubule networks bearing specialized structures for secretion, gas exchange, or filtration. 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 increasing tubule tip numbers through branching and limited organ surface area. Through imaging of whole kidney explants, combined with computational and soft material modeling of tubule families, we identify six possible geometric packing phases, including two defective ones. Experiments in explants show that a radially oriented tension on tubule families is necessary and sufficient for them to switch to a vertical packing arrangement that increases surface tip density while avoiding defects. These results reveal developmental contingencies in response to physical limitations and create a framework for classifying congenital kidney defects.

Topics & Concepts

TubuleBiologyKidneyCell biologyProximal tubuleEpitheliumEmbryonic stem cellFunction (biology)AnatomyBiological systemBiophysicsEndocrinologyGeneticsGeneRenal and related cancersPluripotent Stem Cells ResearchTissue Engineering and Regenerative Medicine
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