How a homogeneous population of cells self-organizes to form a patterned embryo is a long-standing mystery in the field of developmental biology. In 1952, Alan Turing postulated the reaction-diffusion model to explain how embryos might self-organize to develop tissues and organs. The reaction-diffusion model comprises a system of two diffusible substances that must satisfy two requirements in order to form a pattern: (i) one substance activates its own production and is inhibited by the other, and (ii) the diffusivity of the inhibitor has to be higher than the diffusivity of the activator. Genetic and embryological experiments suggest that several patterning events in developing embryos are controlled by reaction-diffusion systems, but a mechanistic, quantitative understanding of how these systems dynamically control robust pattern formation in developing tissues has been lacking.
It has been proposed that the two developmental signals Nodal and Lefty form a reaction-diffusion system during tissue patterning. Within the QUANTPATTERN project, we focused on three key questions about how the Nodal/Lefty system leads to patterning. First, how do activator/inhibitor pairs such as Nodal and Lefty achieve their different diffusivities despite their high sequence similarity and similar molecular weights? Second, how does the range of reaction-diffusion systems such as Nodal and Lefty adjust to natural fluctuations in embryo size? Finally, how do reaction-systems such as Nodal and Lefty self-organize to induce spatially restricted tissues in the absence of pre-patterns?
The QUANTPATTERN project used a combination of quantitative experimental and theoretical approaches to address these questions and had three major aims:
Aim 1: Identify the factors regulating the dispersal of Nodal and Lefty during zebrafish development
Aim 2: Determine how the Nodal/Lefty system mediates scale-invariant patterning of zebrafish embryos
Aim 3: Quantitative analysis of self-organized patterning in mouse embryonic stem cells
