Abstract：
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.
摘要：
分支形态发生是许多重要器官的特征，比如肺和肾，和大多数腺体，并且是两种组织行为的净结果:分支点起始和伸长。每个分支器官都有针对其生理功能而定制的独特结构，但是在这些分支管状结构中如何形成图案是发展的一个基本问题。这里,我们使用定量3D形态计量学，延时成像，操纵离体培养的小鼠胚胎器官和缺乏平面细胞极性成分Vangl2的小鼠，以解决发育中的乳腺中的这个问题。我们的结果表明，由于灵活使用了两种不同的分支点起始模式：侧向分支和尖端分叉，胚胎上皮树的拓扑结构高度复杂。这种非刻板印象与显著恒定的平均分支频率形成对比，表明导管生长不变，然而随机的，分支倾向。分支的可能性是有延展性的,并且可以通过操纵Fgf10和Tgfβ1途径来调节。最后,我们的体内数据和离体延时成像提示乳腺分支延长过程中涉及组织重排.
