Nature Materials ( IF 37.2 ) Pub Date : 2024-10-09 , DOI: 10.1038/s41563-024-02019-3 Louis S. Prahl, Jiageng Liu, John M. Viola, Aria Zheyuan Huang, Trevor J. Chan, Gabriela Hayward-Lara, Catherine M. Porter, Chenjun Shi, Jitao Zhang, Alex J. Hughes
Urinary collecting tubules form during kidney embryogenesis through the branching of the ureteric bud epithelium. A travelling mesenchyme niche of nephron progenitor cells caps each branching ureteric bud tip. These ‘tip domain’ niches pack more closely over developmental time and their number relates to nephron endowment at birth. Yet, how the crowded tissue environment impacts niche number and cell decision-making remains unclear. Here, through experiments and mathematical modelling, we show that niche packing conforms to physical limitations imposed by kidney curvature. We relate packing geometries to rigidity theory to predict a stiffening transition starting at embryonic day 15 in the mouse, validated by micromechanical analysis. Using a method to estimate tip domain ‘ages’ relative to their most recent branch events, we find that new niches overcome mechanical resistance as they branch and displace neighbours. This creates rhythmic mechanical stress in the niche. These findings expand our understanding of kidney development and inform engineering strategies for synthetic regenerative tissues.
中文翻译:
发育中的小鼠肾脏中形成肾单位的生态位的堵塞会产生周期性机械应力
尿集合管在肾胚胎发生过程中通过输尿管芽上皮的分支形成。肾单位祖细胞的移动间充质生态位覆盖每个分枝输尿管芽尖。这些 “尖端域 ”生态位在发育过程中更加紧密地排列,它们的数量与出生时的肾单位禀赋有关。然而,拥挤的组织环境如何影响生态位数量和细胞决策仍不清楚。在这里,通过实验和数学建模,我们表明生态位堆积符合肾曲率施加的物理限制。我们将堆积几何形状与刚性理论联系起来,以预测小鼠从胚胎第 15 天开始的硬化转变,并通过微观力学分析验证。使用一种方法来估计尖端域相对于其最近的分支事件的“年龄”,我们发现新的生态位在分枝并取代邻居时克服了机械阻力。这会在生态位中产生有节奏的机械应力。这些发现扩展了我们对肾脏发育的理解,并为合成再生组织的工程策略提供了信息。