Davies Jamie A, Hohenstein Peter, Chang C-Hong, Berry Rachel
University of Edinburgh, Edinburgh, EH8 9XB, UK.
The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, UK.
BMC Dev Biol. 2014 Sep 10;14:35. doi: 10.1186/s12861-014-0035-8.
Glandular organs require the development of a correctly patterned epithelial tree. These arise by iterative branching: early branches have a stereotyped anatomy, while subsequent branching is more flexible, branches spacing out to avoid entanglement. Previous studies have suggested different genetic programs are responsible for these two classes of branches.
Here, working with the urinary collecting duct tree of mouse kidneys, we show that the transition from the initial, stereotyped, wide branching to narrower later branching is independent from previous branching events but depends instead on the proximity of other branch tips. A simple computer model suggests that a repelling molecule secreted by branches can in principle generate a well-spaced tree that switches automatically from wide initial branch angles to narrower subsequent ones, and that co-cultured trees would distort their normal shapes rather than colliding. We confirm this collision-avoidance experimentally using organ cultures, and identify BMP7 as the repelling molecule.
We propose that self-avoidance, an intrinsically error-correcting mechanism, may be an important patterning mechanism in collecting duct branching, operating along with already-known mesenchyme-derived paracrine factors.
腺器官需要发育出具有正确模式的上皮树。这些上皮树通过反复分支形成：早期分支具有固定的解剖结构，而后续分支则更具灵活性，分支相互散开以避免缠绕。先前的研究表明，不同的基因程序负责这两类分支。
在此，我们以小鼠肾脏的集合管树为研究对象，发现从最初固定的宽分支向较窄的后续分支的转变与先前的分支事件无关，而是取决于其他分支尖端的接近程度。一个简单的计算机模型表明，分支分泌的一种排斥分子原则上可以生成一个间隔良好的树，该树会自动从宽的初始分支角度转变为较窄的后续分支角度，并且共培养的树会扭曲其正常形状而不是相互碰撞。我们通过器官培养实验证实了这种避免碰撞的现象，并确定骨形态发生蛋白7（BMP7）为排斥分子。
我们提出自我避免，一种内在的纠错机制，可能是集合管分支中一种重要的模式形成机制，与已知的间充质衍生旁分泌因子共同起作用。
