Neurons of the central nervous system possess very diverse morphologies, neurotransmitter identities, electrical properties and preferences for synaptic partners. How are all these different properties specified and maintained? We are applying the new Targeted DamID (TaDa) (Southall et al., 2013) technique to profile the transcriptional state of specific neuronal populations in vivo, with the aim of identifying key transcriptional regulators. A comparison of cholinergic, GABAergic and glutamatergic neurons has revealed a number of transcription factors that are specific or highly enriched in the respective cell types. Initial characterisation of candidates has identified an Ets transcription factor that inhibits cholinergic fate. Furthermore, our TaDa data suggests that this type of cross-repressive mechanism might be common for neurotransmitter specification and maintenance.
We are also interested in dedifferentiation in the nervous system, and are investigating the mechanisms by which the transcription factor Lola prevents neurons reverting to a neural stem cell fate (Southall et al., 2014). Interestingly, we have recently identified a small ORF peptide, encoded by a long non-coding RNA, which interacts with Lola and may regulate its function.