title: Modelling chemotactic motion of cells in biological tissue with applications to embryogenesis
Creators: name: Harrison, Nigel
Publisher: name: University of Liverpool Repository
Year: 2013

description: Perhaps one of the most amazing events that occurs in nature, is in the emergence and growth of biological life. Emergence speaks of the well-coined phrase Primordial ooze from which the chemical building blocks of life first gave rise to the complicated molecular structure of Deoxyribonucleic acid (DNA), that has the mind boggling task of encoding every chemical and physical attribute and trait of the organism for which it is encoded. This incredible feat of nature is only equalled by the ability of single fertilized cell (zygote) to undergo a seemingly magical transformation through enlargement, growth and change to give rise to a fully formed animal (or plant). The study and body of knowledge of this latter process is called Developmental Biology, and it seeks to define and explain all of the intricate sub-stages and bio-chemical, molecular and physical processes along the time-line of this transformation, that is from fertilization to birth, hatching or germination and beyond. One might consider, and quite reasonably, that the variety of different processes leading to the development of a complete biological organism would be so vast as to render the problem untenable. Indeed the almost inconceivable amount of genetic information contained within the nucleus of the simplest of cells would seem to corroborate this assumption. However when one takes a more holistic view, we can see that the development of any complex biological organism can be reduced to a set of five distinct processes, all of which are orchestrated to define structures from a body of cells. Viewed in this light the generation of any complex multi-cellular organism, be it small or large, must involve: cell-division, differentiation, pattern formation, change in form and growth [1]. To mediate and orchestrate these different processes during the development of the embryo are a enumerable number of bio-chemicals that are produced within the cells that can diffuse into the surrounding environment, activating (and de-activating) inter/intra-cellular signalling pathways that trigger further productions and possibly one or more of the processes suggested above. One such case of this, and which is of particular interest in this thesis, is in the role of morphogens in the growth of vertebrate embryos, where it is known that interacting morphogen gradients can give rise to spatially stable concentrations [2] that are known to be involved in organ growth [3], primitive streak formation [4] and the extension and patterning of the primary body axis [5, 6, 7]. In this thesis we are considering one such problem involving these mechanisms/processes, during the primary body axis extension in the chick embryo. During this phase of development the early brain is beginning to form and the central nervous system (CNS) is beginning to extend unilaterally in a posterior direction defining the main anteroposterior (head to tail) body axis; in simple terms one may see this as the generation of the spinal cord and surrounding structures. Extension of this axis is known to be orchestrated by a small cellular structure located at the posterior-most tip of the extension, encompassing what is known as the primary organising centre in the chick embryo: Hensen’s node. This structure including the node is known to move independently/autonomously of the rest of the embryo and as it does so the cells in the region are growing and proliferating, and ultimately differentiating and leaving this region to literally fuel the axial extension. This broad description leads us to the heart of our thesis, and which will preoccupy the rest of this dissertation. We postulate that the motile behaviour of the group is as a result of biochemical gradients to which the group is attracted toward areas of highest concentration or towards areas of lowest concentration of some as yet unnamed morphogen. That is we assume that the group moves as a result of a chemotaxis. Furthermore, the growth and subsequent differentiation of cells exiting the group, contributing to the growth of the CNS, are also regulated by the same morphogen. Therefore we propose that a singular bio-chemical mechanism can account for the motile and growth behaviour observed during CNS extension.