Inst. of Cell Biology - Institute Associated Research Group - Developmental Mechanodynamics
We are interested in the following questions that are central to understand the role of MT cytoskeleton in tissue morphogenesis:
(I) What are the structural and mechanical properties of non-centrosomal MTs in wing epithelial cells?
(II) How does MT mechanics contribute to shape changes and cell rearrangements during wing tissue remodeling?
(III) What is the molecular mechanism that integrates and coordinates MT forces across a tissue?
Mechanobiological quantification of microtubule mechanical properties during Drosophila wing morphogenesis
In order to reshape a tissue, force generation must exceed mechanical resistance, thus global patterns of force generation and tissue stiffness jointly dictate speed and direction of tissue rearrangements. The main focus of our studies is on the microtubule cytoskeleton. We investigate the mechanical and structural properties of apical non-centrosomal MTs nucleated at adherens junctions. For this we are using new optical and chemical tools (live imaging, caged MT drugs, laser ablation, FRAP, FRET based tension sensors) in conjunction with classical genetic approaches.
The quantitative data obtained with the mechanobiological approach are correlated with results obtained from quantitative image analysis of developing wing epithelium to study how mechanobiological properties of MTs contribute to cell shape changes and cell-cell contact remodeling.
Figure. 1 Model of MT-based biomechanical forces regulating tissue geometry.
Based on the molecular machinery employed, one can equally well envision that MT-based forces are employed to narrow as well as to elongate the tissue along the polarized MT-axis (A) Polarized protrusive forces contribute to tissue elongation via coordinated cell movement. (B) Polarized pushing or contractile forces bias oriented exchanges of neighboring cells and alter tissue geometry.
Mechanical coupling of microtubules with adherens junctions
Tissue morphogenesis often requires collective cell behaviour. Only the integration of locally produced forces into a global tissue force pattern determines the resulting changes in cell and tissue shape. One of the principal signalling pathways coordinating individual cell dynamics to generate large tissue-scale rearrangements during morphogenesis is planar cell polarity (PCP). We recently showed that the PCP signalling pathway is capable of globally patterning MT cytoskeleton during epithelium development to coordinate local cell behaviours. This analysis and further examples from Drosophila, highlight the importance of MT patterning in promoting coordinated cell behaviour during tissue rearrangements. These studies suggest that apical non-centrosomal MTs nucleated at adherens junctions contribute to epithelial tissue morphogenesis via coordinated generation and integration of local, cell-based forces into a global tissue force pattern (collective mechanics).
To decipher the molecular mechanism that couples MTs with adherens junctions we are using proteomic approach in combination with Drosophila genetics to identify candidate proteins involved in association/nucleation of MTs with adherens junctions.
Dr. Maja Matis