We will provide knowledge and resources to facilitate rigorous assessment and understanding of normal brain development and neuronal differentiation as well as phenotypes affecting nervous system formation, function and viability. This will be achieved at two levels:
- Through mapping of neural gene / transgene expression domains at high resolution to neuroanatomical structures that will enable us to utilise digital 3D gene expression information to correlate neural mutant phenotypes with gene expression patterns; and
- through neuroanatomical dissection of brain circuits underlying the behaviours that will be assessed in WP2, particularly focusing on limbic system pathways and the modulation and output of dopaminergic and serotonergic circuitry.
Our primary approaches will be to conduct high-resolution 3D imaging of neural gene expression domains (using fluorescent whole mount in situ hybridisation) as well as of transgene expression in the wildtype zebrafish brain. We will select neural genes and transgenes that have expression spatially restricted to discrete neuronal populations focusing upon those that are implicated in disease (WP3) and / or in behaviours used for the detailed phenotypic characterisation of novel mutants (WP2) and embryos resulting from treatment with small molecules / drugs (WP5).
This work will predominantly involve ALU-FR (Germany), UCL and KCL (UK). Both ALU-FR (Germany) and UCL (UK) have already performed substantial preliminary work towards these aims in ZF-MODELS, and have established suitable microscopy facilities and image analysis tools.
(Work Package Leader: UCL)