How Do Carbohydrates Instruct Brain Development

The process of the brain developing from a single fertilised cell to the most sophisticated known organ requires complex processes occurring at precise time points. An area of particular interest for researchers is cortex development. In order for generation of optimal cortical architecture and size, individual cells within a population must behave heterogeneously. While it is well established that instructions for development are transmitted to cells by signalling molecules, they are global signals secreted to large groups of cells. However population dynamics and single cell behaviours differ with individual cells exposed to the same signalling molecules exhibiting different responses. In order to understand how the complete system of neural development works we must also understand how cells behave individually.
This project focuses on the Erk signalling cascade, a signalling pathway critical to development, which is involved in controlling cell fate of cortical progenitors. We have identified heterogeneity in Erk activation between neighbouring cells in the proliferative zone of the cortex and seek to understand the impact of this on cell fate. We are utilising a classical staining approach to correlate the level of Erk activation with markers of cell state at a single-cell level at different developmental stages. The overall aim is to develop a model of the impact heterogeneous cellular response to signalling molecules has on controlling cell fate and the complexity of cortical architecture in the developing mouse brain.
It is not only the levels of Erk activation that impact cell fate, but also the time period of activation, a period of minutes rather than days. While the classical staining approach provides a great deal of information, it is a snapshot in time. As the dynamics of Erk activation affect cellular phenotype, understanding its activation kinetics is essential to understanding its role. We are utilising novel reporters of Erk activation to investigate the kinetics of Erk in cortical progenitors using live imaging techniques. Elucidating this will provide much novel information into the importance of Erk activation in the developing cortex.