Development of Epithelium Apical Polarity: Does the mechanical cell-cell adhesions play a role?

ended

One fundamental question in biology is how are epithelial tubes polarised from initially unpolarised cells to establish coherent tissues. In this project, I will determine the role of cell-cell adhesion mediated force during de novo polarisation of epithelial tubes. I will use two models for the studies of this project. First, I will use a mouse embryo stem cell (mESC) culture model that phenocopies the morphogenesis of the very early mammalian embryo during implantation, when the epiblast forms a centrally located, polarised lumen. This minimal model will allow me to control cell number and cell-cell interaction so that I can analyse the initiation of absolutely naïve junctional adhesions in relation to polarisation. Second, I will use the zebrafish neural tube as an in vivo model of epithelial tube formation. I will use a cutting-edge optogenetic approach to both image and manipulate the process of apicobasal polarisation and junctional formation at the single cell level within a whole vertebrate organ. This will also allow me to compare whether the principles driving polarisation are conserved across different systems. I will carry out this research project under the supervision of Clare Buckley at University of Cambridge. During this project, I will have a perfect chance to apply my knowledge in epithelium cell biology into the studies of vertebrate development, and benefit from expertise across disciplines to establish my network and research filed for my future career. The studies of this project will extend our understanding of the biological importance of cell adhesions and advance our knowledge of the fundamental principles of tissue patterning during development. A better understanding of polarisation during development may help us to understand dysregulation of cell polarity in diseases.