Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell & Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Dev Cell. 2023 Jan 23;58(2):110-120.e5. doi: 10.1016/j.devcel.2022.12.008.
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.
几个器官的生理功能依赖于分支的上皮管状网络,这些网络具有专门的结构用于分泌、气体交换或过滤。对于在为充分的功能构建足够的管状结构和由器官大小施加的几何约束之间的发展冲突,我们知之甚少。我们表明,小鼠胚胎肾上皮通过分支来增加管状尖端数量,并在增加管状尖端数量与器官表面积有限之间的物理包装冲突中进行协商。通过对整个肾脏外植体的成像,结合管状家族的计算和软物质建模,我们确定了六个可能的几何包装阶段,包括两个有缺陷的阶段。外植体实验表明,管状家族的径向张力是它们切换到垂直包装排列的必要且充分的条件,这种排列可以增加表面尖端密度,同时避免缺陷。这些结果揭示了对物理限制的发展必然性,并为分类先天性肾脏缺陷创建了一个框架。