論文 - 詳細
| RRC ID | 56199 |
|---|---|
| 著者 | Masoudi N, Tavazoie S, Glenwinkel L, Ryu L, Kim K, Hobert O. |
| タイトル | Unconventional function of an Achaete-Scute homolog as a terminal selector of nociceptive neuron identity. |
| ジャーナル | PLoS Biol |
| Abstract |
Proneural genes are among the most early-acting genes in nervous system development, instructing blast cells to commit to a neuronal fate. Drosophila Atonal and Achaete-Scute complex (AS-C) genes, as well as their vertebrate orthologs, are basic helix-loop-helix (bHLH) transcription factors with such proneural activity. We show here that a C. elegans AS-C homolog, hlh-4, functions in a fundamentally different manner. In the embryonic, larval, and adult nervous systems, hlh-4 is expressed exclusively in a single nociceptive neuron class, ADL, and its expression in ADL is maintained via transcriptional autoregulation throughout the life of the animal. However, in hlh-4 null mutants, the ADL neuron is generated and still appears neuronal in overall morphology and expression of panneuronal and pansensory features. Rather than acting as a proneural gene, we find that hlh-4 is required for the ADL neuron to function properly, to adopt its correct morphology, to express its unusually large repertoire of olfactory receptor-encoding genes, and to express other known features of terminal ADL identity, including neurotransmitter phenotype, neuropeptides, ion channels, and electrical synapse proteins. hlh-4 is sufficient to induce ADL identity features upon ectopic expression in other neuron types. The expression of ADL terminal identity features is directly controlled by HLH-4 via a phylogenetically conserved E-box motif, which, through bioinformatic analysis, we find to constitute a predictive feature of ADL-expressed terminal identity markers. The lineage that produces the ADL neuron was previously shown to require the conventional, transient proneural activity of another AS-C homolog, hlh-14, demonstrating sequential activities of distinct AS-C-type bHLH genes in neuronal specification. Taken together, we have defined here an unconventional function of an AS-C-type bHLH gene as a terminal selector of neuronal identity and we speculate that such function could be reflective of an ancestral function of an "ur-" bHLH gene. |
| 巻・号 | 16(4) |
| ページ | e2004979 |
| 公開日 | 2018-4-1 |
| DOI | 10.1371/journal.pbio.2004979 |
| PII | pbio.2004979 |
| PMID | 29672507 |
| PMC | PMC5908064 |
| MeSH | Animals Basic Helix-Loop-Helix Transcription Factors / genetics* Basic Helix-Loop-Helix Transcription Factors / metabolism Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Computational Biology Electrical Synapses / metabolism Electrical Synapses / ultrastructure Embryo, Nonmammalian Gene Expression Regulation, Developmental* Gene Ontology Ion Channels / genetics Ion Channels / metabolism Larva / cytology Larva / genetics Larva / growth & development Larva / metabolism Molecular Sequence Annotation Neuropeptides / genetics Neuropeptides / metabolism Neurotransmitter Agents / metabolism Nociceptors / cytology Nociceptors / metabolism* Phenotype Receptors, Odorant / genetics Receptors, Odorant / metabolism Transcription, Genetic |
| IF | 8.386 |
| 引用数 | 7 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 16 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm604 tm1688 |