Gilmour Group

Previous and Current Research

Morphogenesis is the generation of complex biological form through coordinated changes in the size, shape and positioning of groups of cells. The guided migration of cohesive groups of cells is a hallmark of embryonic morphogenesis. While such collective migrations determine the shape of most organ systems and are a common feature of wound repair, regeneration and cancer, they are still poorly understood.

The zebrafish lateral line primordium is a migrating cluster of some two hundred cells whose function is to generate and disperse mechanosensory organs throughout the embryonic skin. Cells in this moving tissue must multitask – they migrate, grow, divide and differentiate simultaneously. The lateral therefore provides a powerful model system for addressing how complex form arises through the interplay of basic cellular behaviours. In recent years we have developed a number of in vivo imaging and perturbation tools that allow this entire morphogenetic process to be addressed at sub-cellular resolution in the context of the intact, living embryo.

Genetic screens have lead to the isolation of a number of signalling molecules required for primordium migration. The primordium is guided by the chemokine Sdf1 and its receptor Cxcr4, a signalling pathway that is known to regulate the invasive behaviour of many human tumours. Furthermore, cells within the primordiumare assembled into rosette-like organ progenitors via a dynamicmesenchymal-epithelial transition that is driven through spots of FGF-ligand that repeatedly appear within the tissue as it migrates.

Future Projects and Goals

Our aim is to understand how changes in cellmigration and morphology spread across moving tissues during organogenesis.We are developing quantitative imaging methods that allow us to precisely measure the activity of Cxcr4/Sdf1, FGF and other key chemical signalling systems with the aim of elucidating how local changes in activity drive differences in cell behaviour. As these signalling systems exert their effect via the cytoskeleton and cell cortex, we are also using a complementary, ‘bottom-up’ approach that addresses how local changes cytoskeletal dynamics regulate cell-cell interactions within tissues. Using biophysical tools such as laser ablation in combination with advanced 3D imaging, we hope to address the role of mechanical forces in coordinating cell behaviour. These quantitative data are being used to support the formulation of mathematicallymodels that will accurately simulate this complex in vivo morphogenesis process.