Abstract

“Although the nervous systems of probably all bilaterian animals are left right asymmetric, we know relatively little about how such asymmetries are established or encoded in neural circuits. Research from our lab has helped to establish the zebrafish as a good model in which to study the development of brain asymmetry. We have shown that breaking of symmetry and allocation of handedness to the asymmetry are separable processes and that Nodal, Wnt and Fgf pathways together break symmetry and determine its laterality. Complementing genetic studies, we are analyzing the developmental neuroanatomy of the brain, particularly with respect to asymmetric circuitry. For instance, we have shown that the left and right habenular nuclei project to different regions of their target nucleus, and that for individual neurons, left-right asymmetry is manifest as differences in axon terminal morphology and targeting.

These neuroanatomical studies underpin research that aims to link circuitry to neuronal activity and behaviour. One major challenge is to identify complex behaviours that are sufficiently robust to be amenable to both genetic and neuroanatomical interrogation. To this end, we, and others, are developing assays for simple learning and fear responses and social interactions in fry. Coupled to analysing behaviour, our lab is using genetic/optogenetic approaches to interrogate neuronal activity in lateralised brain nuclei. We have recently found that the left and right habenulae respond to different sensory stimuli and that loss of brain asymmetry impairs the ability to respond to such stimuli. The long-term goal of our research is to be able to move from genes through developmental mechanisms to circuits and behaviour in the intact developing animal.

The UCL zebrafish website will give you more details of some of our lab’s research projects and publications (www.ucl.ac.uk/zebrafish-group/).”