Zentralprojekt

中央项目

• 批准号: 258605532
• 负责人: Professor Dr. Jörg Großhans
• 金额: --
• 依托单位: Arbeitsgruppe Entwicklungsgenetik
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/258605532?language=en
• 关键词: Zentralprojekt

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

组织形态发生调控的一个核心要素是物理细胞-细胞接触的形成、重排和维持，这是由粘附分子和细胞表面配体/受体系统介导的（Yamada 2007）。该研究单位（FOR）将专注于定义和分析细胞组件和小细胞组中细胞接触的功能动力学。动态的细胞接触决定了特定的细胞行为，并构成了组织延伸、细胞重排、细胞迁移、神经元-胶质和肌肉-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，但可能会成为相关的后续行动。这些研究将在一组遗传上可处理的模型系统中进行，包括果蝇、秀丽隐杆线虫、爪蟾和斑马鱼的胚胎，这些胚胎可以通过生物物理和显微镜方法获得。由于分子和形态变化的动态，以及多种过程和细胞类型协同作用的事实，细胞行为一直难以分析。近年来，新的细胞动力学和形态学检测方法和指标已经解决了部分这些问题。除了遗传方法（如RNAi基因耗尽，CRISPR/TALEM位点特异性基因工程）和使用荧光蛋白的活体显微镜（Giepmann2006），生物物理学（如原子力显微镜，m<e:1>勒尔2009，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，Rauzi2008)将被纳入，以更好地理解动态细胞行为和细胞组装背景下细胞接触依赖过程的共同机制原则。除了理解形态发生的细胞基础的学术动机外，这些见解对于理解器官形成和器官功能是如何由分子水平上的细胞相互作用控制的最终至关重要。这将进一步与未来的医学相关，特别是考虑到实验分化干细胞的潜力日益增长（Eiraku2011, Lancaster2013, Sasai2013），在可预见的未来，这可能允许在体外产生任何给定的细胞类型。与这些观点相反，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，不仅局限的多细胞组装，而且整个器官组装的原理和机制都必须被剖析。结合不断发展的干细胞技术，这些知识可能最终允许在实验和治疗上重建从干细胞到特定细胞的所有步骤