Modeling of Wnt-mediated tissue patterning in vertebrate embryogenesis

摘要

How entire organisms develop out of single cells is a long-term challenge in the life sciences. Morphogens are crucial signaling molecules organizing cell fates and patterning by their local concentrations. While many morphogens diffuse freely, specialized cell extrusions can facilitate directed cell-to-cell transport for morphogens of the Wnt/ -Catenin family. We performed simulations of quickly growing tissue take this into account, back to back with in-vivo experiments. Our simulations suggest that stochasticity effects lead to non-physiological fluctuating boundaries of tissue regions if not properly controlled. Such control can be achieved via directed cell sorting and apoptosis. We provide experimental evidence for both mechanisms. We observe a distinct temporal difference between the transport mechanisms, with cytonemes facilitating an earlier establishment of a stable pre-pattern. Overall, simulations suggest that cytoneme-mediated Wnt transport is advantageous over diffusion-based transport and a potential general mechanism to establish morphogen gradients in rapidly expanding developmental systems.