The developing kidney actively negotiates geometric packing conflicts to avoid defects

Prahl, L.; Viola, John M.; Liu, Jiageng; Hughes, Alex J.

doi:10.1101/2021.11.29.470441

Cited by 8 publications

(20 citation statements)

References 42 publications

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“…1A ). We previously noted an analogy for close packing of caps in the physics of repulsive or elastic particles at surfaces (18). Repulsive particles pack most efficiently on flat surfaces in a hexagonal close-packed (triangular lattice) fashion where each particle has six neighbors (i.e.…”

Section: Resultsmentioning

confidence: 99%

“…One-way ANOVA, Tukey’s test: *p < 0.05, **p < 0.01, ***p < 0.001). ( E ) Left column , Representative physical model output for tubule packing regimes characteristic of the indicated developmental ranges, previously reported in (18). Right column , overlays of Delauney triangulations indicating coordination number of tip domains on spatial heatmaps of shape index, showing reducing shape index as tip patterns transition from amorphous to square-like to hcp-like regimes.…”

Section: Resultsmentioning

confidence: 99%

“…Immunofluorescence staining and imaging was performed as previously described (18), using protocols adapted from Combes et al . and O’Brien et al .…”

Section: Methodsmentioning

confidence: 99%

“…Kidney immunofluorescence imaging. Immunofluorescence staining and imaging was performed as previously described (18), using protocols adapted from Combes et al and O'Brien et al (94,95). Briefly, dissected kidneys were fixed in ice cold 4% paraformaldehyde in DPBS for 20 min, washed three times for 5 min per wash in ice cold DPBS, blocked for 2 hr at room temperature in PBSTX (DPBS + 0.1% Triton X-100) containing 5% donkey serum (D9663, Sigma), incubated in primary and then secondary antibodies in blocking buffer for at least 48 hr at 4 o C, alternating with 3 washes in PBSTX totaling 12-24 hours.…”

Section: Methodsmentioning

confidence: 99%

“…1B for schematic purposes only. Quantitative principles of this software environment are detailed in (18). We used the SphereCollide goal to model sphere mutual repulsion and the OnMesh goal to hold spheres at flat or larger spherical interfaces, each with arbitrarily high energy potential weightings to mimic previously described features of particle packings on surfaces (19)(20)(21)97).…”

Section: Methodsmentioning

confidence: 99%

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Tubule jamming in the developing mouse kidney creates cyclical mechanical stresses in nephron-forming niches

Viola

Liu

Prahl

et al. 2022

Preprint

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Immunofluorescence staining and imaging was performed as previously described (18), using protocols adapted from Combes et al . and O’Brien et al .…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Tubule jamming in the developing mouse kidney creates cyclical mechanical stresses in nephron-forming niches

Viola

Liu

Prahl

et al. 2022

Preprint

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A Guide Toward Multi-scale and Quantitative Branching Analysis in the Mammary Gland

Hannezo

Scheele

2023

Cell Migration in Three Dimensions

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The mammary gland consists of a bilayered epithelial structure with an extensively branched morphology. The majority of this epithelial tree is laid down during puberty, during which actively proliferating terminal end buds repeatedly elongate and bifurcate to form the basic structure of the ductal tree. Mammary ducts consist of a basal and luminal cell layer with a multitude of identified sub-lineages within both layers. The understanding of how these different cell lineages are cooperatively driving branching morphogenesis is a problem of crossing multiple scales, as this requires information on the macroscopic branched structure of the gland, as well as data on single-cell dynamics driving the morphogenic program. Here we describe a method to combine genetic lineage tracing with whole-gland branching analysis. Quantitative data on the global organ structure can be used to derive a model for mammary gland branching morphogenesis and provide a backbone on which the dynamics of individual cell lineages can be simulated and compared to lineage-tracing approaches. Eventually, these quantitative models and experiments allow to understand the couplings between the macroscopic shape of the mammary gland and the underlying single-cell dynamics driving branching morphogenesis.

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How to build an epithelial tree

Paramore¹,

Goodwin²,

Nelson³

2022

Phys. Biol.

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Nature has evolved a variety of mechanisms to build epithelial trees of diverse architectures within different organs and across species. Epithelial trees are elaborated through branch initiation and extension, and their morphogenesis ends with branch termination. Each of these steps of the branching process can be driven by the actions of epithelial cells themselves (epithelial-intrinsic mechanisms) or by the cells of their surrounding tissues (epithelial-extrinsic mechanisms). Here, we describe examples of how these mechanisms drive each stage of branching morphogenesis, drawing primarily on studies of the lung, kidney, salivary gland, mammary gland, and pancreas, all of which contain epithelial trees that form through collective cell behaviors. Much of our understanding of epithelial branching morphogenesis comes from experiments using mice, but we also include examples here from avian and reptilian models. Throughout, we highlight how distinct mechanisms are employed in different organs and species to build epithelial trees. We also highlight how similar morphogenetic motifs are used to carry out conserved developmental programs or repurposed to support novel ones. Understanding the unique strategies used by nature to build branched epithelia from across the tree of life can help to inspire creative solutions to problems in tissue engineering and regenerative medicine.

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The developing kidney actively negotiates geometric packing conflicts to avoid defects

Cited by 8 publications

References 42 publications

Tubule jamming in the developing mouse kidney creates cyclical mechanical stresses in nephron-forming niches

Tubule jamming in the developing mouse kidney creates cyclical mechanical stresses in nephron-forming niches

A Guide Toward Multi-scale and Quantitative Branching Analysis in the Mammary Gland

How to build an epithelial tree

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