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

在组织形态发生的调节中相关性和局部性元素是由粘合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）。研究单元（FOR）将集中于定义和分析细胞组件和小细胞集中细胞接触的功能动力学。动态细胞接触确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-GLIA和肌肉 - 刺激性相互作用的驱动力。目前尚无FOR的更复杂的问题，例如器官形成，通过扩散因素或细胞 - 矩阵相互作用的相互作用，但可能与该计划的后续行动相关。该研究将在一组遗传上可触发的模型系统中进行，包括Drosophila，C。exequans，Xenopus，Xenopus和Zeebrafish bioscorsial and Ictical and Ictical and Ictical and Ictical and Ictical and Ictical and Ictical and Iccoptic and Iccoptic and Iccoptic and Iccoptic and conteriation。由于分子和形态学变化的动力学，并且由于多个过程和细胞类型协同作用，因此很难分析细胞行为。近年来，这些问题的一部分已通过新的分析和形态学指标解决。 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 sensitivity-ECIS, Giaever1993, cell tension and force测量结果，Landsberg2010，Maitre2012）和理论方法（Farhadifar2007，Rauzi2008）将被合并，以更好地理解细胞接触过程的常见机械原理，以动态细胞行为和细胞组件的方式了解细胞的动机，从而使学术的序列依次了解，从而确定了序言，从而确定了形成的序言，从而确定了形式的形式。器官形成和器官功能受分子水平的细胞相互作用控制。这将进一步具有未来的医学相关性，特别是鉴于实验区分干细胞的潜力越来越不断增长（Eiraku2011，Lancaster2013，Sasai2013），这在可预见的将来可以允许在体外生成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佳。从长远的角度来看，不仅必须剖析了限制的多细胞组件，而且还必须解剖整个器官的原理和机制。结合扩展的干细胞技术，这种知识最终可以实验和治疗地重建从干细胞到特定细胞的所有这些步骤，