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http://purl.uniprot.org/citations/22069471http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22069471http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22069471http://www.w3.org/2000/01/rdf-schema#comment"

Background

In most animal species, males and females exhibit differences in behavior and morphology that relate to their respective roles in reproduction. DM (Doublesex/MAB-3) domain transcription factors are phylogenetically conserved regulators of sexual development. They are thought to establish sexual traits by sex-specifically modifying the activity of general developmental programs. However, there are few examples where the details of these interactions are known, particularly in the nervous system.

Methodology/principal findings

In this study, we show that two C. elegans DM domain genes, dmd-3 and mab-23, regulate sensory and muscle cell development in a male neural circuit required for mating. Using genetic approaches, we show that in the circuit sensory neurons, dmd-3 and mab-23 establish the correct pattern of dopaminergic (DA) and cholinergic (ACh) fate. We find that the ETS-domain transcription factor gene ast-1, a non-sex-specific, phylogenetically conserved activator of dopamine biosynthesis gene transcription, is broadly expressed in the circuit sensory neuron population. However, dmd-3 and mab-23 repress its activity in most cells, promoting ACh fate instead. A subset of neurons, preferentially exposed to a TGF-beta ligand, escape this repression because signal transduction pathway activity in these cells blocks dmd-3/mab-23 function, allowing DA fate to be established. Through optogenetic and pharmacological approaches, we show that the sensory and muscle cell characteristics controlled by dmd-3 and mab-23 are crucial for circuit function.

Conclusions/significance

In the C. elegans male, DM domain genes dmd-3 and mab-23 regulate expression of cell sub-type characteristics that are critical for mating success. In particular, these factors limit the number of DA neurons in the male nervous system by sex-specifically regulating a phylogenetically conserved dopamine biosynthesis gene transcription factor. Homologous interactions between vertebrate counterparts could regulate sex differences in neuron sub-type populations in the brain."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0026811"xsd:string
http://purl.uniprot.org/citations/22069471http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0026811"xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Bian X."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Bian X."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Bunkers M.R."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Bunkers M.R."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Koo P.K."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Koo P.K."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Lints R."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Lints R."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Miller R.M."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Miller R.M."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Portman D.S."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Portman D.S."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Sherlekar A.L."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Sherlekar A.L."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Siehr M.S."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/author"Siehr M.S."xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/name"PLoS ONE"xsd:string
http://purl.uniprot.org/citations/22069471http://purl.uniprot.org/core/name"PLoS ONE"xsd:string
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