The Biomechanics of Intercalation in Germ-Band Elongation

 描述（由申请人提供）：在发育过程中使用的主要组织成形机制之一是组织伸长，这对于形成伸长的头-尾体轴和许多内脏器官的发育至关重要。在上皮片层中，驱动细胞-细胞粘附局部变化的细胞过程可以被发育程序利用，以影响组织结构的宏观变化，如伸长;一个例子是果蝇生殖带上皮的系统性重塑。 流行的模型是，连接相关蛋白的平面极性系统驱动连接重塑的必要破坏;具体地说，已经提出，由肌动球蛋白收缩产生的线张力驱动具有特定空间取向的细胞-细胞界面的收缩和损失。为了更详细地描述这一过程的生物力学特征，我们正在用定量成像和分析方法测量连接收缩和生长的动态;根据我们的初步结果，我们假设连接不是通过张力收缩重塑，而是通过“滑动”型位移。 由于细胞拓扑结构和蛋白质动力学在组织伸长过程中迅速变化，我们正在开发新的计算方法，以允许从连接顶点到细胞和整个组织的水平分析重塑行为。 这些应当是科学界广泛感兴趣的分析工具。在这些研究中使用的方法将借鉴先进的成像，计算和生物物理技术，这些技术刚刚开始应用于果蝇。该项目的资助将是新成立的实验室的第一笔主要赠款，并将代表建立独立研究项目的重要一步。

 DESCRIPTION (provided by applicant): One of the primary tissue shaping mechanisms that is utilized during development is tissue elongation, which is essential to the formation of the elongated head-to-tail body axis and to the development of many internal organs. In epithelial sheets, cellular processes that drive local changes in cell-cell adhesion can be harnessed by developmental programs to effect macroscopic changes in tissue architecture such as elongation; one example is the systematic remodeling of the germ-band epithelium in drosophila. The prevailing model is that a system of planar polarity of junction-associated proteins drives the necessary symmetry-breaking of junction remodeling; specifically, it has been proposed that line tension generated by actomyosin contraction drives the shrinking and loss of cell-cell interfaces with specific spatial orientation. To develop a more detailed biomechanical characterization of this process, we are measuring the dynamics of junction contraction and growth with quantitative imaging and analytical methods; based on our preliminary results, we hypothesize that junctions remodel not through tension contraction, but through `sliding' type displacement. Since cell topologies and protein dynamics are rapidly changing during tissue elongation, we are developing novel computational approaches to permit the analysis of remodeling behaviors from the level of junction vertices to cells and whole tissue. These should be analytic tools of broad interest to the scientific community. The approaches used in these studies will draw on advanced imaging, computational and biophysical techniques that are just beginning to be applied in Drosophila. The funding of this project will be the first major grant for the newly established lab, and will represent an important step towards the founding of independent research programs.