Pattern Formation During Extensive Cell Movements

Abstract

As embryos develop, they are required to generate organised patterns of gene expression across developing tissues. Previous hypotheses used to explain how patterns form in developing tissues have relied on the ideas of positional information and gradients of signalling across the developing tissue, which impart spatial coordinates to individual cells. These coordinates then inform the cell of its respective fate, and hence a pattern of gene expression with spatial organisation is generated. This way of thinking about the problem of pattern formation has been highly successful in explaining the patterning of tissues in vertebrate embryos. However, such an approach begins to fail when challenged with tissues where the cells which make it are highly motile.

This thesis will examine the extent to which patterning is robust to cell mixing by disrupting early positional information prior to gastrulation, using whole embryonic explants which undergo widespread cell mixing. These explants elongate, form all three germ layers with spatial organisation and anteroposterior patterned neural tissue. This thesis will then examine the robustness of patterning within the presomitic mesoderm, where a posterior to anterior pattern of gene expression is observed despite high levels of cell rearrangement. Within this tissue, the pattern is observed to accurately scale to the shortening anterior to posterior length and is demonstrated to be highly robust to changes in the degree of cell mixing following experimental perturbation, including in vitro culture of individual cells and pharmacological treatment.

Together, this thesis will argue that to understand pattern formation in tissues which are also undergoing extensive cell rearrangement, it is important to consider the gene regulatory network dynamics and how these are influenced by signalling. Rather than taking a positional information “bottom up” type view of cell fate decision making, where signalling gradients inform cells of their position and hence their identity, I will argue for a more holistic approach to understanding development. By considering how “top down” regulation of patterning, mediated via the movement of cells and tissues between domains of signalling, it will be demonstrated that pattern formation can be considered an emergent properly of cells, regulated by signalling as well as cell movements.