The asymmetric brain: from genes to circuits and behaviour. (360G-Wellcome-089227_Z_09_Z)

Asymmetry is a fundamental, yet poorly understood, feature of the CNS, critical for efficient cognitive function and disrupted in various neuropathologies. We have established the larval zebrafish as a powerful model for studying many aspects of CNS asymmetry. Our goals for this programme of research are to resolve the mechanisms by which symmetry is broken, to determine how concordance between neuroanatomical asymmetries is achieved, to elucidate the circuitry into which asymmetric neurons a re incorporated and to link activity in asymmetric circuits to behaviour. Fgf signalling is required for the leftward migration of the parapineal and we will determine how activation of this pathway is localised to leading cells of the migrating primordium. We will also address whether and how, this activation is dependent upon localised Nodal signalling. Subsequent to migration, the parapineal imposes asymmetry upon the left habenula and we will clone novel mutations in which this comm unication is disrupted and will resolve the role of Wnt signalling in this process. We will use powerful transgenesis techniques to resolve the circuitry of the epithalamic nuclei and will refine assays for behaviours that are influenced by neuroanatomical lateralisation. Finally we will directly link circuit activity to behaviour in free-swimming fry.