Jean-Paul Vincent group

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.

Figure 1

Figure 1

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Impaired Wingless secretion on VPS35 mutants. The Wingless gradient fails to form and Wingless accumulates in producing cells.

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 or loss of cell adhesion leads to extensive apoptosis. Also, abnormal differences in growth rates between neighboring cells 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.

Figure 2

Figure 2

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An apoptosis sensor. The top panel shows the design of the sensor, which is tethered to membranes in live healthy cells. Upon caspase activation, the green moiety is released and targeted to the nucleus. The bottom panel shows cultured cells either exposed to UV irradiation to trigger apoptosis (right) or mock treated (left). Note the accumulation of GFP in the nucleus of dying cells.

Movie 1

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Massive disruption of the epidermis and extensive apoptosis in crumbs-/- embryos. Nuclei are green and membranes red. Note macrophages (red) engorged with dead epithelial cells at the end of the movie.

Selected publications

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