Development of the metanephric kidney

Smyth, Ian

doi:10.1016/bs.ctdb.2020.09.003

Cited by 5 publications

(3 citation statements)

References 212 publications

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“…We also observed dislocations and disclinations between aligned regions, which are hallmarks of liquid crystals and elastic crystalline solids ( 13 , 14 ). These data and published accounts of a lack of stereotypy ( 7 , 15 ) argue against a strict morphogenetic control program and instead for tip patterns being determined by competition between crowding and repulsion.…”

Section: Main Textmentioning

confidence: 68%

“…1B), so the eventual filtration and reabsorption function of the adult kidney likely scales with the number of tips. However, while some organs like the lung fill 3D space during branching, ureteric branching occurs at the kidney surface (6)(7)(8). This should create a conflict between the available organ surface area and exponentially increasing tip number (Supplementary Text).…”

mentioning

confidence: 99%

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The developing kidney actively negotiates geometric packing conflicts to avoid defects

Prahl

Viola

Liu

et al. 2021

Preprint

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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

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Section: Main Textmentioning

confidence: 68%

mentioning

confidence: 99%

The developing kidney actively negotiates geometric packing conflicts to avoid defects

Prahl

Viola

Liu

et al. 2021

Preprint

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“…A better understanding would also inform in vitro synthetic kidney tissue production using organoids, where contemporary protocols produce nephrons in a single inductive wave rather than in sustained waves 7,8 . In vivo , nephron progenitor (‘cap mesenchyme’) niches balance renewal vs. differentiation by interpreting autonomous cues and those from adjacent ureteric bud and stromal cell populations 9 ( Fig. 1A,B ).…”

Section: Introductionmentioning

confidence: 99%

Nephron progenitors rhythmically alternate between renewal and differentiation phases that synchronize with kidney branching morphogenesis

Davis,

Grindel,

Viola

et al. 2023

Preprint

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The mammalian kidney achieves massive parallelization of function by exponentially duplicating nephron-forming niches during development. Each niche caps a tip of the ureteric bud epithelium (the future urinary collecting duct tree) as it undergoes branching morphogenesis, while nephron progenitors within niches balance self-renewal and differentiation to early nephron cells. Nephron formation rate approximately matches branching rate over a large fraction of mouse gestation, yet the nature of this apparent pace-maker is unknown. Here we correlate spatial transcriptomics data with branching ‘life-cycle’ to discover rhythmically alternating signatures of nephron progenitor differentiation and renewal across Wnt, retinoic acid (RA), Hippo-Yap and other pathways. We then reveal stark differences in progenitor renewal vs. differentiation rates depending on whether Yap is activated in- or out-of-phase with Wnt/β-catenin-induced differentiation of human stem-cell derived nephron progenitor organoids. Our data brings temporal resolution to the renewal vs. differentiation balance in the nephrogenic niche, and informs new strategies to achieve self-sustaining niches in synthetic human kidney tissues.

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

et al. 2023

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Development of the metanephric kidney

Cited by 5 publications

References 212 publications

The developing kidney actively negotiates geometric packing conflicts to avoid defects

The developing kidney actively negotiates geometric packing conflicts to avoid defects

Nephron progenitors rhythmically alternate between renewal and differentiation phases that synchronize with kidney branching morphogenesis

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

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