論文 - 詳細
| RRC ID | 46499 |
|---|---|
| 著者 | Siehr MS, Koo PK, Sherlekar AL, Bian X, Bunkers MR, Miller RM, Portman DS, Lints R. |
| タイトル | Multiple doublesex-related genes specify critical cell fates in a C. elegans male neural circuit. |
| ジャーナル | PLoS One |
| 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. 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. |
| 巻・号 | 6(11) |
| ページ | e26811 |
| 公開日 | 2011-1-1 |
| DOI | 10.1371/journal.pone.0026811 |
| PII | PONE-D-11-11110 |
| PMID | 22069471 |
| PMC | PMC3206049 |
| MeSH | Animals Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Dopaminergic Neurons / cytology* Dopaminergic Neurons / metabolism Female Male Muscle, Skeletal / cytology* Muscle, Skeletal / metabolism Neurotransmitter Agents / metabolism Sensory Receptor Cells / cytology* Sensory Receptor Cells / metabolism Signal Transduction |
| IF | 2.74 |
| 引用数 | 19 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY |
| リソース情報 | |
| 線虫 | tm2863 |