A tumour forming in a Drosophila epithelium

Research Overview

The Thompson Lab uses Drosophila as a model organism to investigate both normal tissue development and tumour formation.  We focus on the epithelial tissues of the fly, particularly on the developing wing and eye.  

We are interested in two major questions:

• How is the growth of an epithelial tissue controlled?
• What determines the architecture of an epithelium?

Tissue Growth

Tissues grow in a precisely controlled way to produce adult structures of the correct size.  To achieve this, the growth and division of individual cells must be tightly regulated by intercellular signaling pathways that organise tissue development.  

Several important signaling pathways that control size in Drosophila have been identified, including secreted morphogens (such as Wnt / Wingless and TGF-beta / Decapentaplegic) and hormonal signals (such as Insulin-like peptides).  Mis-regulation of these pathways can lead to tumour-like overgrowths in Drosophila and to cancer in humans.

Genetic screens in Drosophila recently uncovered several new players, such as the Hippo signaling pathway and a microRNA called bantam.  In collaboration with Nic Tapon's lab, we are interested in how these different pathways interact to control the growth of Drosophila tissues.

Epithelial architecture

When cells construct tissues, the forms they generate depend upon the shapes of individual cells and how those cells connect to one another.  In epithelial tissues, cells are polarised along an apical-basal axis and are connected via adherens junctions to form a sheet of cells. 

Most human tumours are epithelial in origin and tumour cells must acquire the ability to escape the epithelium in order to progress to metastasis.

We are identifying genes required for epithelial cells to maintain their polarity, shape and adhesive contacts.  We recently discovered a new Drosophila tumour suppressor gene, vps25, whose loss causes cells to lose their apical-basal polarity and overproliferate to form large metastatic tumours.

Future Projects

We are conducting an in vivo genome-wide RNAi screen in the Drosophila wing to identify key molecules regulating tissue growth and epithelial morphology.  We will combine genetics with cell biology to explore how these molecules act within systems that determine organ size and epithelial architecture.