The ability to easily perform screens for mutants that affect reporter gene expression in the nervous system and the ability to decode cis-regulatory modules in transgenic animals are among the key reason why C. elegans is our favorite model system to study neuronal gene regulatory mechanisms. However, we are also much interested in studying whether gene regulatory mechanisms that we are uncovering in the worm are conserved across phylogeny.
We have already shown that gene regulatory mechanisms that control dopaminergic neuron specification are conserved from C.elegans to mouse [1] and we have shown, in collaboration with Mike Levine’s lab at UC Berkeley, that gene regulatory mechanisms controlling cholinergic motor neuron specification are conserved from C.elegans to at least a simple chordate, Ciona intestinalis [2].
We are currently expanding our forays in vertebrate neurobiology by investigating whether we can also define terminal selector-type transcription factors in the vertebrate nervous system. We are specifically going after vertebrate orthologs of C.elegans terminal selectors and use classic mouse genetic approaches, such a Cre-mediated, temporally controlled knockout strategies to define transcription factor function in terminal differentiation events in the nervous system.
Staying closer to home, we have also investigated how regulatory mechanisms that control left/right asymmetry in the nervous system are conserved in other nematodes [3] and we consider expanding these studies. We are particularly interested in the question of how evolvable terminal differentiation programs are.
Bibliography:
1. Flames, N. & Hobert, O. Gene regulatory logic of dopamine neuron differentiation. Nature 458, 885-9 (2009).
2. Kratsios, P., Stolfi, A., Levine, M. & Hobert, O. Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene. Nat Neurosci 15, 205-14 (2011).
3. Ortiz, C.O. et al. Searching for neuronal left/right asymmetry: genomewide analysis of nematode receptor-type guanylyl cyclases. Genetics 173, 131-49 (2006).