title: Multiple doublesex-related genes specify critical cell fates in a C. elegans male neural circuit.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors: Department of Biology, Texas A & M University, College Station, Texas, United States of America.
authors: Meagan S
authors: MS
authors: Siehr
authors: Pamela K
authors: PK
authors: Koo
authors: Amrita L
authors: AL
authors: Sherlekar
authors: Xuelin
authors: X
authors: Bian
authors: Meredith R
authors: MR
authors: Bunkers
authors: Renee M
authors: RM
authors: Miller
authors: Douglas S
authors: DS
authors: Portman
authors: Robyn
authors: R
authors: Lints
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism; D005260:Female; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; C532001:DMD-3 protein, C elegans; D004268:DNA-Binding Proteins; C110548:Mab-3 protein, C elegans; D018377:Neurotransmitter Agents