Patterning and homeostasis in developing epithelia

Our general approach is to use Drosophila as a model system to study basic cell biological mechanisms that are relevant to human cancers. Drosophila gives us two main advantages: we can use the latest methods of molecular genetics and we are able to examine the behaviour of cells within their normal tissue environment. We focus on two main issues: How is the range and activity of Wnts, a family of signaling molecules, regulated and how are weak or mispecified cells recognised and eliminated from epithelia.

Trafficking and Wnt gradient formation

Although misregulation of Wnt signaling is often associated with cancer, the normal function of Wnts is to orchestrate cell fate decisions during development. We investigate the mechanisms that control the production and spread of this important signal. In addition to studying the cell biology basis of Wnt gradient formation, we also investigate how this signal controls patterning, growth and cell death.

Some of our recent achievements include uncovering the role of retrograde transport in Wnt secretion, characterising the role of endocytosis in Wnt signalling, demonstrating that Wnts do not necessarily need to spread and showing that Notum suppresses Wnt activity by enzymatically removing an essential lipid moiety.

Anti-wingless immunostaining of the basal surface of a wing imaginal disc.

Anti-wingless immunostaining of the basal surface of a wing imaginal disc.

Elimination of defective cells by apoptosis

In a second strand of work, we are exploring how defective/weak cells are detected and eliminated from tissues. For example, loss of cell polarity, loss of cell adhesion and removal of essential patterning genes all cause extensive apoptosis. Abnormal differences in growth rates between neighboring cells can also lead to the death of slow growing cells. We want to decipher the mechanisms that link basic features such as cell polarity, adhesion, growth rate and cell fate to the apoptotic machinery. We have been focusing particularly on the role of JNK signaling and on the transcriptional activation of the pro-apoptotic genes hid and reaper and we have recently shown that Shnurri, a mediator of Dpp signaling protects the dorsal epidermis from JNK-mediated activation of reaper.

Above: Widespread apoptosis (visualised through activated caspase staining in green) is observed in a pattern corresponding to that of wild-type gene expression in an embryo mutant for the pair rule gene fushi tarazu. Below: Wild type and schnurri mutant embryos imaged by SPIM (single plane illumination microscopy) and viewed from 8 angles during germband extension and dorsal closure.