Using the zebrafish as a model, the Gilmour group takes an integrative, multiscale approach to study how cells collectively migrate and assemble into functional organs.
Figure 1: The zebrafish migrating lateral line organ allows collective migration to be easily studied in vivo.
Figure 2: Visualising actin dynamics (LifeAct-GFP) within migrating primordium.
Previous and current research
Collective behaviour lies at the heart of all biological design. Whether it is the assembly of proteins into complexes or the organisation of animal societies, collective interaction creates something much greater than the sum of the parts. A breathtaking example of such behaviour is seen during embryogenesis, when thousands of collectively migrating cells self-organise to form functional tissues and organs. Given the key role played by collective migration in organ formation, wound repair and cancer, it is surprisingly how little we know about how cells organise each other.
We take an integrative, multi-scale approach to study how cells collectively migrate and assemble into functional organs, using the zebrafish lateral line organ as an experimental model. Here, a migrating epithelial primordium comprising of 100 cells, assembles and deposits a series of rosette-like mechanosensory organs across the surface of the embryo. Its superficial migration route, beneath a single transparent cell layer, makes it the dream in vivo sample for quantitative imaging. Moreover, the process can be interrogated using a range of perturbation approaches, such as chemical and optogenetics, and many of the molecular regulators of its migratory behaviour are of general interest due to their role in human disease. For example, the migrating collective is guided by Cxcr4/SDF1 signalling, a chemokine-receptor pair known to control many human cancers.
Future projects and goals
The focus of our group is to use the lateral line to address the general question of how cell behaviours are regulated and coordinated within collectively migrating tissues. We have developed in vivo imaging, analysis and perturbation tools that allow the entire morphogenesis process to be addressed at different spatiotemporal scales. By integrating these data, using statistical methods and modelling, we are aiming to understand the interplay between ‘opposing’ behaviours – namely, cell migration and differentiation. In this way, we hope to move towards a systems-level understanding of how dynamic cell organisation and gene expression are integrated during tissue morphogenesis.