Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, Helsinki 00014, Finland.
Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 90014, Finland.
Development. 2024 Aug 1;151(15). doi: 10.1242/dev.202179. Epub 2024 Aug 2.
Branching morphogenesis is a characteristic feature of many essential organs, such as the lung and kidney, and most glands, and is the net result of two tissue behaviors: branch point initiation and elongation. Each branched organ has a distinct architecture customized to its physiological function, but how patterning occurs in these ramified tubular structures is a fundamental problem of development. Here, we use quantitative 3D morphometrics, time-lapse imaging, manipulation of ex vivo cultured mouse embryonic organs and mice deficient in the planar cell polarity component Vangl2 to address this question in the developing mammary gland. Our results show that the embryonic epithelial trees are highly complex in topology owing to the flexible use of two distinct modes of branch point initiation: lateral branching and tip bifurcation. This non-stereotypy was contrasted by the remarkably constant average branch frequency, indicating a ductal growth invariant, yet stochastic, propensity to branch. The probability of branching was malleable and could be tuned by manipulating the Fgf10 and Tgfβ1 pathways. Finally, our in vivo data and ex vivo time-lapse imaging suggest the involvement of tissue rearrangements in mammary branch elongation.
分支形态发生是许多重要器官（如肺和肾以及大多数腺体）的特征，是分支点起始和伸长两种组织行为的净结果。每个分支器官都有独特的结构，适应其生理功能，但在这些分支管状结构中如何发生模式形成是发育的一个基本问题。在这里，我们使用定量的 3D 形态计量学、延时成像、离体培养的小鼠胚胎器官的操作以及平面细胞极性成分 Vangl2 缺失的小鼠来解决乳腺发育过程中的这个问题。我们的结果表明，由于灵活使用两种不同的分支点起始模式：侧向分支和尖端分叉，胚胎上皮树具有高度复杂的拓扑结构。这种非定型性与平均分支频率的显著恒定性形成对比，表明导管生长具有不变但随机的分支倾向。分支的概率是可塑的，可以通过操纵 Fgf10 和 Tgfβ1 途径来调节。最后，我们的体内数据和离体延时成像表明组织重排可能参与了乳腺分支伸长。
