Neural Network Development Group ongoing projects
Signals of change and mechanisms of maintenance
To identify the signals that instruct change during the critical period, we successfully adopted a best candidate approach and targeted genetic screens. We are now seeking a more detailed mechanistic understanding of how these signals operate. Related, we are working with collaborators, Jelle van den Ameele (MRC-Mitochondrial Biology Unit) and Tony Southall (Imperial College, London), to ask how such transient signals convert to lasting changes in gene expression and cellular properties. Here, we think that changes in epigenetic chromatic modifications are key, investigated using chromatin-DamID.
Epigenetic marks in muscle nuclei (yellow) change following different embryonic critical period experiences (nerves in magenta; actin in cyan). Enlarged inset shows muscle nucleus and chromatin DamID analysis strategy.
Network connectivity is shaped by critical periods of development
In the central nervous system, transient embryonic experiences during the critical period determine nerve cell growth and connectivity. We visualise these adaptations by high resolution imaging of fluorescent protein markers. Imaging of structural changes is complemented by electrophysiological approaches, conducted here and in collaboration with the Richard Baines group at the University of Manchester. This combined approach allows us to understand how nervous systems compensate for disturbances during development, so as to robustly generate appropriate function and behaviour.
Expression patterns of specific neuron types within the central nervous system of the Drosophila larva (left and right). Detailed view of a specific motoneuron (gold) and the pattern of synaptic input sites (blue).