3D reconstruction of a chick embryo heart

This project is now closed

Molecular mechanisms of boundary formation by Eph receptor and ephrin signaling

Project supervisor: David Wilkinson (Developmental Neurobiology)

The generation of precisely organised tissues during development requires the restriction of intermingling and formation of sharp borders between distinct cell populations. In some tissues, borders have key roles in pattern formation as they serve as signaling centres that regulate cell differentiation. The correct segregation of cells is also required to maintain tissue organisation in the adult, and if disrupted during tumour progression leads to the metastatic spreading of cancer cells. Identification of the underlying molecular mechanisms will thus give important insights into normal development and disease.

In previous studies, we uncovered a mechanism of border formation mediated by signaling between Eph receptors and ephrins. This mechanism is widely utilised in many tissues, including the developing hindbrain where it is required to establish the correct organisation of boundaries, neural progenitors and differentiating neurons. Further understanding requires elucidation of the intracellular pathways activated by Eph-ephrin signaling that underlie border formation. To address this we have developed amenable cell culture assays of border formation that enable identification of intracellular targets of Eph receptor activation and analysis of their function.

The aim of the project is to elucidate the roles of targets of Eph receptor and ephrin signaling in border formation by using a combination of in vitro and in vivo assays. The in vivo studies will use the major advantages of the zebrafish model for application of genetic and reverse genetic techniques to investigate the roles of genes, combined with live imaging to visualise cell migration. To facilitate these studies, we have developed powerful tools using Gal4-based gene trap lines to achieve localised transgene expression, and multicolour transgenic labelling of cells for visualisation of cell behaviour and lineage analysis.

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