Deanery of Biomedical Science, University of Edinburgh, Edinburgh, UK.
Yale University School of Medicine, Medicine, New Haven, CT, USA.
J Anat. 2019 Aug;235(2):262-270. doi: 10.1111/joa.13012. Epub 2019 May 17.
The path taken by the loop of Henle, from renal cortex to medulla and back, is critical to the ability of the kidney to concentrate urine and recover water. Unlike most developing tubules, which navigate as blind-ended cylinders, the loop of Henle extends as a sharply bent loop, the apex of which leads the double tubes behind it in a 'V' shape. Here, we show that, in normal kidney development, loops of Henle extend towards the centroid of the kidney with an accuracy that increases the longer they extend. Using cultured kidney rudiments, and manipulations that rotate or remove portions of the organ, we show that loop orientation depends on long-range cues from the medulla rather than either the orientation of the parent nephron or local cues in the cortex. The loops appear to be attracted to the most mature branch point of the collecting duct system but, if this is removed, they will head towards the most mature collecting duct branch available to them. Our results demonstrate the adaptive nature of guidance of this unusual example of a growing epithelium, and set the stage for later work devoted to understanding the molecules and mechanisms that underlie it.
亨利氏袢从肾皮质延伸到髓质再回到皮质的路径对于肾脏浓缩尿液和回收水分的能力至关重要。与大多数发育中的肾小管不同，亨利氏袢呈急剧弯曲的环，其尖端在后面的双管以“V”字形领先。在这里，我们表明，在正常的肾脏发育过程中，亨利氏袢向肾脏的质心延伸，延伸的长度越长，精度越高。使用培养的肾脏原基和旋转或切除部分器官的操作，我们表明环的方向取决于来自髓质的长程线索，而不是母体肾单位的方向或皮质中的局部线索。这些环似乎被吸引到收集管系统最成熟的分支点，但如果这个分支点被去除，它们将朝向最成熟的收集管分支前进。我们的结果证明了这种生长上皮的不寻常引导方式的适应性，并为以后致力于理解其基础的分子和机制的工作奠定了基础。
