To study how cells communicate with each other, we use the segmenting vertebrate embryo as model system of embryonic development and the growing small intestine as model system of adult tissue maintenance. To study tissue maintenance, we make use of so-called organoids or mini-organs, culture systems that can be grown in the lab and recapitulate key aspects of the respective organ. Critical steps in this investigations are (1) the visualization of signalling activities within single cells in the context of an entire tissue and (2) the functional analysis of cell-cell communication. To address these points, we have initiated the following:
1. For the visualization of this cell-cell communication we use available and have generated new signalling reporter lines that emit fluorescence when communication pathways are active. We have also generated combinations of reporters that either report on different signalling pathways and cell fate. Moreover, we have optimized real-time imaging of our model systems and detection and quantification of these fluorescent reporters.
2. To understand how cells communicate with each other and especially how cells use dynamic changes to transmit information, we have to be able to subtly modulate this communication and analyze the effect of this modulation. We have set up and optimized a microfluidic system that allows us to culture our model systems, segmenting embryo tissue and mini-organs, in small incubation chambers - termed chips - and apply pulses of pathway modulators with high precision. This allows us to subtly change the observed pathway activity and then analyze the effect on development and growth.
