Regulation of cell behaviour and identity in a branching epithelium

• Main Author: Sweeney, Derina E.
• Published: University of Edinburgh 2006
• Subjects: 611
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662659

Although differentiation and morphogenesis of the ureteric bud have been studied for many years, the mechanisms that control their overall pattern remain unknown. In this thesis, I have tested a specific set of hypotheses in which both differentiation and morphogenesis are controlled by a self-organization based on inhibitory interactions between tip and stalk cells. Using micro dissection and ex-vivo organ culture I show that: 1. The ureteric bud is composed of at least two distinct populations of cells, those that bind Dolichos biflorus agglutinin (DBA) and those that do not. These correspond to the stalk and tip regions respectively. DBA seems to be a marker of regions of the ureteric bud in which branching morphogenesis is inactive. 2. Using DBA to detect tip cells, I investigated the mechanisms controlling branching of the ureteric bud. Firstly, the hypothesis that branches rarely arise from the stalks of the ureteric bud because they have lost the ability to branch was tested; it seems that the stalk cells retain their ability to behave as tips when provided with an appropriate environment. Differentiation of ureteric bud cells is therefore surprisingly plastic. 3. I also tested the hypothesis that tips of the ureteric bud space out relative to each other by sensing and responding to tips in the local vicinity. There are two components to this hypothesis: (i) that tips are separated within an epithelium by a lateral inhibition mechanism that prevents new tips forming close to existing ones, and (ii) that tips of extending epithelia are repelled by the presence of nearby tips, so that they spread out to fill space optimally. I have gained supporting evidence against the first hypothesis as tips will form stalk regions whether tips are preformed or not elsewhere in the epithelium. The data presented in this thesis provide evidence both to partially support, and also to limit, the specific self-organisation hypothesis tested.