In order to construct tissues of particular forms, cells must be able to orient their behaviour relative to one another. We examine the molecular determinants of cell polarity and how these determinants orient cell behaviour in vivo.
The relevance of this work for human disease is illustrated by the fact that defects in systems of cell polarity can lead to developmental abnormalities and tumour formation.
We focus particularly on the epithelial tissues of the fruit fly, Drosophila, which offers the possibility of live-imaging of epithelial tissue development as well as powerful genetic analysis. We also apply computational modelling of cell polarity and tissue morphogenesis to understand the principles that govern polarisation of determinants and how these determinants can influence cell shape, cell division, cell migration and tissue morphogenesis.The laboratory uses both Drosophila and mice as model organisms to explore how cells construct epithelial tissues during development and how epithelial tumours can arise. We focus on the question of how cell polarity organises the behaviour of cells within an epithelium.
We take three main approaches:
- Genetic analysis of gene functions in vivo.
- Live-imaging of epithelial tissue development.
- Computational modelling of cell polarity and cell behaviour.
We aim to combine these approaches to identify molecular mechanisms responsible for organising cell polarity and cell behaviour during tissue growth and morphogenesis in epithelia. Our recent work has examined two different types of cell polarity in epithelia, apico-basal polarity and planar polarity.
In apical-basal polarity, we focus on the role of apical determinants such as Crumbs, Bazooka, Cdc42, Par6 and aPKC and basolateral determinants such as Lgl, Dlg and Scrib. These molecules control the polarisation of all other proteins and organelles in epithelial cells. Disruption of epithelial polarity is a feature of advanced adenocarcinomas, suggesting that apical-basal polarity determinants may have an important role in human cancer.
In planar polarity, we focus on the role of the Dachsous-Fat system, which is responsible for orienting tissue growth to elongate tissues in both Drosophila and mice. We have characterised how this system becomes planar polarised and how it can influence tissue mechanics to orient cell divisions and tissue growth.
Both the apical-basal and planar polarity systems are able to influence signalling through the Hippo pathway, which acts via Yki/YAP/TAZ to control cell proliferation. We are interested in understanding the physiological roles of Hippo signalling as a sensor of epithelial cell polarity and mechanical forces in both Drosophila and mice.