Skip to main content

Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene

Author(s): Kratsios, Paschalis; Stolfi, Alberto; Levine, Michael S.; Hobert, Oliver

To refer to this page use:
Abstract: Cholinergic motor neurons are defined by the coexpression of a battery of genes encoding proteins that act sequentially to synthesize, package and degrade acetylcholine and reuptake its breakdown product, choline. How expression of these critical motor neuron identity determinants is controlled and coordinated is not understood. We show here that, in the nematode Caenorhabditis elegans, all members of the cholinergic gene battery, as well as many other markers of terminal motor neuron fate, are co-regulated by a shared cis-regulatory signature and a common trans-acting factor, the phylogenetically conserved COE (Collier, Olf, EBF)-type transcription factor UNC-3. UNC-3 initiated and maintained expression of cholinergic fate markers and was sufficient to induce cholinergic fate in other neuron types. UNC-3 furthermore operated in negative feedforward loops to induce the expression of transcription factors that repress individual UNC-3-induced terminal fate markers, resulting in diversification of motor neuron differentiation programs in specific motor neuron subtypes. A chordate ortholog of UNC-3, Ciona intestinalis COE, was also both required and sufficient for inducing a cholinergic fate. Thus, UNC-3 is a terminal selector for cholinergic motor neuron differentiation whose function is conserved across phylogeny.
Publication Date: 27-Nov-2011
Citation: Kratsios, Paschalis, Stolfi, Alberto, Levine, Michael S., Hobert, Oliver. (2011). Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene. Nature Neuroscience, 15 (2), 205 - 214. doi:10.1038/nn.2989
DOI: doi:10.1038/nn.2989
ISSN: 1097-6256
EISSN: 1546-1726
Pages: 205 - 214
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Nature Neuroscience
Version: Author's manuscript

Items in OAR@Princeton are protected by copyright, with all rights reserved, unless otherwise indicated.