Zentralprojekt

相关性和局部性调节组织形态发生的一个中心要素是由黏附分子和细胞表面配体/受体系统介导的物理细胞-细胞接触的形成、重排和维持(Yamada 2007)。研究单位(FOR)将重点定义和分析蜂窝组件和小电池组中电池接触的功能动力学。动态的细胞接触决定了特定的细胞行为，并构成了组织伸长、细胞重排、细胞迁移、神经元-胶质细胞和肌肉-肌腱相互作用的驱动力。更复杂的问题，如器官形成，通过扩散因子的细胞-细胞相互作用，或细胞-基质相互作用，目前不是FOR的重点，但可能在这一倡议的后续行动中变得相关。研究将在一系列遗传易处理的模型系统中进行，包括可通过生物物理和显微方法获得的果蝇、秀丽线虫、非洲爪哇和斑马鱼胚胎。由于分子和形态变化的动力学，以及多种过程和细胞类型协同作用的事实，细胞行为很难分析。近年来，通过细胞动力学和形态的新分析和指示剂，这些问题中的一部分已经得到解决。除了遗传方法(例如，RNAi的基因缺失，CRISPR/TALEM的位点特异性基因工程)和使用荧光蛋白的活显微镜(Giepmann 2006)、生物物理学(例如原子力显微镜，Müller2009，电细胞-底物阻抗传感-ECIS，Giaever1993，细胞张力和力测量，Landsberg2010，Maitre2012)和理论方法(Farhadifar2007，Rauzi 2008)外，还将结合这些方法来更好地理解细胞接触依赖过程的共同机制原理，在动态细胞行为和细胞组装的背景下。除了理解形态发生的细胞基础的学术动机之外，这些见解对于理解器官形成、器官形成和力的形成是至关重要的和器官功能，是由分子水平上的细胞相互作用决定的。这将进一步具有未来的医学意义，特别是考虑到在实验上分化干细胞的潜力越来越大(Eiraku 2011，Lancaster2013，Sasai 2013)，在可预见的未来，这可能允许在体外产生任何特定类型的细胞。与这些观点形成对比的是，我们目前对单个细胞如何组装成多细胞结构的理解相当不发达。从长远来看，不仅是有限的多细胞组装，而且是整个器官的组装所依据的原则和机制都必须被剖析。与扩增干细胞技术相结合，这种知识最终可能允许从实验和治疗上重建从干细胞到特定细胞的所有步骤，以及

Relevance and topicalityA central element in the regulation of tissue morphogenesis is the formation rearrangement and maintenance of physical cell-cell contacts, as mediated by adhesion molecules and cell surface ligand/receptor systems (Yamada 2007). The research unit (FOR) will focus on defining and analysing the functional dynamics of cell contacts in cellular assemblies and small sets of cells. The dynamic cell contacts determine specific cellular behaviour and constitute the driving force for tissue elongation, cell rearrangement, cell migration, neuron-glia and muscle-tendon interaction. More complex questions like organ formation, cell-cell interactions via diffusible factors, or cell-matrix interactions are currently no focus of the FOR, but may become relevant in a follow-up of this initiative.The studies will be performed in a set of genetically tractable model systems, including Drosophila, C. elegans, Xenopus and zebrafish embryos that are accessible to biophysical and microscopic methods. Cell behaviour has been difficult to analyse due to the dynamics of the molecular and morphological changes and due to the fact that multiple processes and cell types act in concert. Part of these problems have been solved in recent years by new assays and indicators for cell dynamics and morphology. In addition to genetic methods (e. g. gene depletion by RNAi, site specific genetic engineering by CRISPR/TALEM) and live-microscopy employing fluorescent proteins (Giepmann2006), biophysical (e. g. atomic force microscopy, Müller2009, electrical cell-substrate impedance sensing-ECIS, Giaever1993, cell tension and force measurements, Landsberg2010, Maitre2012) and theoretical approaches (Farhadifar2007, Rauzi2008) will be incorporated to gain a better understanding of the common mechanistic principles of cell contact-dependent processes in the context of dynamic cellular behaviours and cellular assemblies.Besides the academic motivation for understanding the cellular basis of morphogenesis, such insights are ultimately crucial in order to understand how organ formation, and organ function, is governed by cellular interactions at the molecular level. This will further be of future medical relevance, in particular in light of the growing potential to experimentally differentiate stem cells (Eiraku2011, Lancaster2013, Sasai2013), which in the foreseeable future may allow for the generation of any given cell type in vitro. In contrast to these perspectives, our current understanding of how individual cells assemble into multi-cellular structures is rather poorly developed. In the long-term, principles and mechanisms that underlie the assembly not only of circumscribed multicellular assemblies, but also of entire organs, will have to be dissected. In combination with the expanding stem cell technologies, such knowledge may ultimately allow to experimentally and therapeutically reconstitute all those steps that lead from stem cells to specified cells, an