Evolution of Neuronal Regulatory Programs

<p dir="ltr">Neurons are key for organisms to respond to the environment. Monoamines act as neuromodulators to regulate neuronal responses according to context. Monoamines are produced in specific populations of neurons. Monoaminergic neurons are widely distributed across Bilateria. The origin of monoaminergic genes and the homology of monoaminergic neurons remains unknown. In this thesis I will attempt to answer the evolutionary origin of monoaminergic genes. I will use single-cell transcriptomics to investigate the conservation of transcription factors in monoaminergic neurons and attempt to establish their homology. I will extend my analyses to Cnidaria and investigate the conservation of regulatory genes that control the formation of neurons and neuronal structures. I will use Nematostella vectensis as a model organism. I find the orthologs of monoaminergic genes are highly conserved across Bilateria. These genes originate through gene duplications in the bilaterian and eumetazoan ancestors. This indicates that the canonical monoaminergic pathway is a bilaterian innovation. I find high but inconsistent levels of transcription factor similarity across monoaminergic neurons. My results support the homology of some monoaminergic neurons but do not identify a single set of regulatory genes. I find that neurogenic transcription factors are highly conserved in their orthology and expression between N. vectensis and Strongylocentrotus purpuratus as well as other organisms. These include monoaminergic linked transcription factors. Across my analyses I find high levels of conservation across Bilateria and Eumetazoa. The conservation of expression patterns indicates a strong conservatism in gene function. There are step changes in the use of transcription factors and monoaminergic genes at different levels in the phylogenetic tree. These results suggest that a nascent monoaminergic neuron was present in the ancestor of Bilateria which may have co-opted genes and regulatory connections from an older neurogenic program shared across Eumetazoa.</p>