Jamming of nephron-forming niches in the developing mouse kidney creates cyclical mechanical stresses

Prahl, Louis S.; Liu, Jiageng; Viola, John M.; Huang, Aria Zheyuan; Chan, Trevor J.; Hayward-Lara, Gabriela; Porter, Catherine M.; Shi, Chenjun; Zhang, Jitao; Hughes, Alex J.

doi:10.1038/s41563-024-02019-3

Nat. Mater.

2024

DOI: 10.1038/s41563-024-02019-3

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Jamming of nephron-forming niches in the developing mouse kidney creates cyclical mechanical stresses

Louis S. Prahl,

Jiageng Liu,

John M. Viola

et al.

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Engineering kidney developmental trajectory using culture boundary conditions

Huang,

Prahl,

et al. 2024

Preprint

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Kidney explant cultures are traditionally carried out at air-liquid interfaces, which disrupts 3D tissue structure and limits interpretation of developmental data. To overcome this limitation, we developed a 3D culture technique using hydrogel embedding to capture morphogenesis in real time. We show that 3D culture better approximatesin vivo-like niche spacing and dynamic tubule tip rearrangement, as well asin vivo-like presentation of branching defects under perturbations to glial cell-derived neurotrophic factor (GDNF)-REarranged duringTransfection (RET) tyrosine kinase signaling. We find that the concentration of the embedding matrix influences the number of nephrons per ureteric bud (UB) tip and the spacing between tips. To isolate the effect of specific material properties on explant development, we introduce engineered acrylated hyaluronic acid hydrogels that allow independent tuning of stiffness and adhesion. We find that sufficient stiffness and adhesion are both required to maintain kidney shape. Matrix stiffness has a “Goldilocks effect” on the nephron per UB tip balance centered at ∼2 kPa, while higher matrix adhesion increases nephron per UB tip ratio. Our technique captures large-scale,in vivo-like tissue morphogenesis in 3D, providing a platform suited to contrasting normal and congenital disease contexts. Moreover, understanding the impact of boundary condition mechanics on kidney development benefits fundamental renal research and advances the engineering of next-generation kidney replacement tissues.

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Engineering kidney developmental trajectory using culture boundary conditions

Huang,

Prahl,

et al. 2024

Preprint

View full text Add to dashboard Cite

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Jamming of nephron-forming niches in the developing mouse kidney creates cyclical mechanical stresses

Cited by 1 publication

References 62 publications

Engineering kidney developmental trajectory using culture boundary conditions

Engineering kidney developmental trajectory using culture boundary conditions

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