SPP 1782:  Epithelial intercellular junctions as dynamic hubs to integrate forces, signals and cell behaviour

• Subject Area: Biology
• Term: since 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255103767

Epithelia are stable tissues that line organ and body surfaces to provide structural support and serve as barriers against diverse external stressors such as mechanical force, pathogens, toxins, and dehydration. Further, they separate different physiological environments and are instrumental during morphogenesis. These epithelial functions depend to a great extent on the ability of intercellular junctions to sense and integrate mechanical forces and chemical signals. They transmit these into the cell to direct rapid changes in cell architecture and/or transcriptional programming thus directing cellular behaviour. Understanding how intercellular junctions sense their neighbours, force and chemical signals, how such information at these junctions is integrated to elicit cellular responses at a mechanistic level will be central to comprehend control of tissue morphogenesis, homeostasis and regeneration. Further, elucidating how genetic defects in intercellular junction components by-pass junction-mediated control of epithelial tissue integrity is a prerequisite to understand the basis of multiple disorders including blistering skin disorders, inflammation and cancer.The primary goal of the Priority Programme is thus to understand how intercellular junctions sense and respond to mechanical and chemical signals from neighbouring cells and how they convert these signals into processes that underlie epithelial morphogenesis, differentiation and pathogenesis. To this end the Priority Programme invites interdisciplinary approaches that bridge the levels of molecules, cells, tissues and model organisms, combining biophysical, biochemical, cell biological and physiological techniques. Projects should aim at the following goals:- identification of molecules that sense and transmit mechanical force and chemical signals at intercellular junctions, to get insights into downstream signal transmission- integration of mechanical and chemical signals by adherens junctions and desmosomes to regulate cell behaviour and cell fate- understanding at a quantitative level how mechanical force is sensed at intercellular junctions and how it is transmitted into chemical signals- elucidation of the force-dependent crosstalk between intercellular junctions and the cytoskeleton- advancement of biophysical and imaging methods to analyse force and chemical signal transmission via adhesive junctions in tissuesTo foster optimal collaboration between groups, the following projects are explicitly excluded:- work on cytoskeletal proteins not focussing on their interactions with intercellular junctions- analysis of cell-matrix junctions except if they address crosstalk between hemidesmosomes and intercellular junctions- studies on gap and tight junctions except if they investigate potential adhesive functions- descriptive approaches including non-mechanistic studies on disease conditions or animal models- identification or characterisation of adhesive junction-related biomarkers

• DFG Programme: Priority Programmes

Projects

• A role of plakophilin 3 in keratinocyte proliferation (Applicant Hatzfeld, Mechthild )
• Connecting intercellular cell junctions with Hippo/YAP pathway activity in hepatocytes and liver tumor cells (Applicant Breuhahn, Kai )
• Consequences of desmoglein 2 loss for organization and function of intestinal epithelial junctions (Applicant Strnad, Pavel )
• Coordination Funds (Applicant Magin, Thomas )
• Coupling intercellular adhesion, polarity and mechanical signals at epidermal junctions (Applicant Iden, Sandra )
• Deciphering the role of mechanics for epithelia trans-differentiation (Applicant Diz-Muñoz, Alba )
• Desmosome-cytoskeleton dynamics (Applicant Leube, Rudolf E. )
• Force transmission in epithelia - the impact of next neighbors (Applicant Janshoff, Andreas )
• Formin-like 2 associates with the alpha-catenin/E-cadherin complex to control junctional actin dynamics and epithelialization (Applicant Grosse, Robert )
• Functional analysis of the LIM domain protein Smallish in regulation of actomyosin contractility and junctional dynamics at the ZA (Applicant Wodarz, Andreas )
• Integration of cell polarity, cell adhesion and actomyosin dynamics during epithelial morphogenesis (Applicants Grill, Stephan Wolfgang ;  Knust, Elisabeth )
• Intercellular junctions as force integrating anchors during epithelial cell shape transitions (Applicant Classen, Anne-Kathrin )
• Interplay between mechanical tension and cytoskeletal organization in cell separation at compartment boundaries in Drosophila (Applicant Dahmann, Christian )
• Investigating the Mechanical Loading of Desmosomes (Applicant Grashoff, Carsten )
• Keratin-dependent regulation of desmosome composition and actin organization (Applicant Magin, Thomas )
• LASP1 as a functional linker protein between cadherin and actin dynamics at epithelial adherens junctions (Applicant Schnittler, Hans-Joachim )
• Mechanisms of junctional actin organization in epidermal morphogenesis and homeostasis (Applicant Niessen, Carien )
• Mechano-transduction and coordinated dynamics in epithelial cells in the amnioserosa of Drosophila (Applicants Großhans, Jörg ;  Wolf, Fred )
• Mechanobiological Analysis of Microtubule-Based Forces at Epithelial Adherens Junctions During Tissue Morphogenesis (Applicant Matis, Maja )
• Mechanosensation and –response of epidermal systems (Applicants Hoffmann, Bernd ;  Merkel, Rudolf )
• Molecular mechanism of E-Cadherin mediated mechano-sensing (Applicant Gräter, Frauke )
• Molecular mechanism of force-sensing in desmoplakin (Applicant Gräter, Frauke )
• Molecular mechanisms patterning viscosity of the junctional network during Drosophila pupal wing morphogenesis (Applicant Grill, Stephan Wolfgang )
• New functions of Pals1 as a signaling hub at cell-cell contacts (Applicants Krahn, Ph.D., Michael ;  Weide, Thomas )
• Piezo mechanosensitive receptor interplay with tight junction proteins for maintenance of epithelial cell number and integrity (Applicant López Posadas, Ph.D., Rocío )
• Reconstructed cell-cell interfaces with spatially defined mechanical and molecular components: biomimetic microenvironments to elucidate how extracellular mechanochemical signals are sensed and transmitted at the intercellular junctions (Applicant del Campo Bécares, Aránzazu )
• Role of Dsg2-dependent adhesion and signalling in Crohn s disease (Applicants Schlegel, Nicolas ;  Waschke, Jens )
• Role of JAM family adhesion molecules in epithelial cell extrusion (Applicant Ebnet, Klaus Thomas )
• Role of the cell junction-assocaited mechanical forces in the regulation of organ size in zebrafish (Applicant Lecaudey, Virginie )

• Spokesperson: Professor Dr. Thomas Magin