Hufnagel Group
Dynamics of cell growth and tissue architecture
Bridging the scales from a single cell to the whole tissue by combining cell culture and organ growth experiments with modelling.
Previous and current research
Two fundamental processes must occur concurrently in tissues during animal development. Firstly, tissues must grow rapidly to generate the final adult size of the organism, and cells have to stop growing and dividing once the final size is reached. Secondly, the tissue needs to be specified and patterned with each cell adopting the appropriate fate and gene expression profile for its position. Both processes are intrinsically connected and need to be coordinated. Central to the formation of a tissue is the establishment, maintenance and remodelling of complex cell-cell interactions that supply mechanical integrity and stability. Tissue growth is a highly dynamic and heterogeneous process. It involves many spatial and temporal scales, and for a deeper understanding one has to integrate information on a single cell level with cell-cell interactions and population effects.
We have recently investigated the interplay between the growth of Drosophila wing imaginal discs and the formation of the Dpp morphogen gradient. Our results suggest a new scenario of size determination, where disc size is determined relative to the fixed morphogen distribution. Our model shows that a feedback of mechanical stress on cell growth can compensate for non-uniform distributions of growth- stimulating morphogens and insures uniform growth throughout the disc. Furthermore, we have formulated and analysed a model describing the interaction of morphogens with glypicans and have compared its prediction to measurements of the effect of glypican Dally-like (Dlp) overexpression on Wingless (Wg) morphogen signalling in Drosophila wing imaginal discs. The model explains the opposing effect that Dlp overexpression has on Wg signalling in the distal and proximal regions of the disc. Our model suggests that Dlp acts by allowing Wg to diff use on cell surface while protecting it from loss and degradation, and that Dlp, rather than acting as Wg co-receptor, competes with receptors for morphogen binding.
Currently, we are investigating the role of mechanical constraints on cell growth, apoptosis, orientation of division, intra-tissue rearrangements and cell differentiation.
Future projects and goals
Our research interests are focussed on the control and regulation of cell proliferation, apoptosis and cellular rearrangement processes in developing tissues, with a specific emphasis on epithelial tissues and the role of mechanical interactions as a regulator.
We seek to characterise and quantify the spatio-temporal effects of mechanical stress, deformations and fluid flow-induced sheer stress on cell growth, gene expression and cellular polarity in two-dimensional epithelial tissues. To address this issue, we pursue an interdisciplinary approach combining classical biological techniques with detailed modelling methods from various fields, ranging from statistical physics to applied mathematics and computer science. Our research also relies on novel microscopy methods in conjunction with the development of sophisticated image analysis tools. Furthermore, the group continues its current research on Drosophila wing development and has a specific interest in the spread of pathogens in epithelial tissues.