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Projekt
Zentralprojekt
Antragsteller
Professor Dr. Jörg Großhans
Fachliche Zuordnung
Entwicklungsbiologie
Förderung
Förderung von 2014 bis 2018
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 200509276
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
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