Self-Assembly During Animal Development

Abstract

Complex adult tissues develop from single cells during embryonic development. These tissues are formed without instruction from external cues i.e. they are self-assembled. In this thesis, we present novel mathematical methods and experimental results that help us to understand the self-assembly of several different biological tissues. First, we consider the self-organization of periodic patterns – for example, the regularly spaced gene expression stripes that prepattern the fingers in the hand – many of which have been described by Turing’s reaction-diffusion hypothesis. In Chapter 2, we use a generic model of periodic patterning to challenge the prevalence of Turing’s model and instead argue that many tissues could be patterned by cell-based and mechanical mechanisms. In Chapter 3, we extend this theory to consider pattern orientation (i.e. how the direction of a striped pattern is controlled) and suggest three types of mechanism that are broadly applicable. In Chapter 4, we apply these theoretical results to a specific biological question, namely: how are evenly spaced digits (fingers) specified in the hand? We propose a novel model of limb patterning in which the digits are specified as an array of spots, and then elongate into rod-like cartilage elements to form the fingers. In Chapter 5, we consider a completely different way to form a repetitive pattern, using a genetic oscillator coupled to a moving wavefront which converts a temporal oscillation into a spatial periodicity. Such a mechanism has been proposed to explain the rhythmic and sequential formation of somites along the vertebrate backbone, but the precise mechanism was unclear. Using a combination of experiments and modeling, we propose a new, scaling-based model of somitogenesis that reconciles previously inconsistent data, and can fully predict several new experimental perturbations. Finally, in Chapter 6, we move away from patterning and instead focus on the control of cell number as tissues self-assemble. Using high-resolution timelapse imaging and physical perturbations applied to zebrafish embryos, we uncovered a novel feedback mechanism of cell number in the neural tube: regulation of differentiation rate by cell shape and tissue packing.