Signaling dynamics in the control of cell proliferation and differentiation during development and homeostasis

ongoing

Tight coordination between proliferation and differentiation is key to proper development and homeostasis of multicellular systems. Cell-cell communication via signaling pathways has long been studied in this context. Encoding information in the temporal change of a signal, i.e. signaling dynamics, can ensure information transmission to be specific and accurate. Studies exemplifying the relevance of dynamic signaling raise the critical question: What is the function of signaling dynamics in controlling proliferation and differentiation at tissue level? My expertise in signaling dynamics, advanced light microscopy, microfluidics, development, cell cycle research and organoid culture provides a unique skill-set for the functional investigation of dynamic signaling during development and tissue homeostasis using two model systems: Somitogenesis in vertebrate embryos is the sequential segmentation of growing tissue. It is controlled by signaling gradients and oscillations. Whereas differentiation has been studied extensively, it remains elusive (A) how cell proliferation is regulated and (B) whether there is a link between proliferation and signaling dynamics. Indeed, our preliminary data strongly indicate that cell proliferation impacts on signaling oscillations. Homeostasis of adult tissue is also maintained by signaling pathways balancing proliferation and differentiation. In the small intestine some of these pathways have recently been shown to be dynamic. We will apply a systematic approach to understand (A) are signaling pathways in the intestine dynamic and (B) what is the function. Our preliminary data support that combining organoid culture, light-sheet microscopy and microfluidic perturbation allows quantification and functional analysis of signaling dynamics. By comparing signaling dynamics in development and homeostasis we will derive general principles of dynamic signal encoding in multicellular systems.