論文 - 詳細
| RRC ID | 6355 |
|---|---|
| 著者 | Flames N, Hobert O. |
| タイトル | Gene regulatory logic of dopamine neuron differentiation. |
| ジャーナル | Nature |
| Abstract |
Dopamine signalling regulates a variety of complex behaviours, and defects in dopamine neuron function or survival result in severe human pathologies, such as Parkinson's disease. The common denominator of all dopamine neurons is the expression of dopamine pathway genes, which code for a set of phylogenetically conserved proteins involved in dopamine synthesis and transport. Gene regulatory mechanisms that result in the direct activation of dopamine pathway genes and thereby ultimately determine the identity of dopamine neurons are poorly understood in all systems studied so far. Here we show that a simple cis-regulatory element, the dopamine (DA) motif, controls the expression of all dopamine pathway genes in all dopaminergic cell types in Caenorhabditis elegans. The DA motif is activated by the ETS transcription factor AST-1. Loss of ast-1 results in the failure of all distinct dopaminergic neuronal subtypes to terminally differentiate. Ectopic expression of ast-1 is sufficient to activate the dopamine pathway in some cellular contexts. Vertebrate dopamine pathway genes also contain phylogenetically conserved DA motifs that can be activated by the mouse ETS transcription factor Etv1 (also known as ER81), and a specific class of dopamine neurons fails to differentiate in mice lacking Etv1. Moreover, ectopic Etv1 expression induces dopaminergic fate marker expression in neuronal primary cultures. Mouse Etv1 can also functionally substitute for ast-1 in C. elegans. Our studies reveal a simple and apparently conserved regulatory logic of dopamine neuron terminal differentiation and may provide new entry points into the diagnosis or therapy of conditions in which dopamine neurons are defective. |
| 巻・号 | 458(7240) |
| ページ | 885-9 |
| 公開日 | 2009-4-16 |
| DOI | 10.1038/nature07929 |
| PII | nature07929 |
| PMID | 19287374 |
| PMC | PMC2671564 |
| MeSH | Animals Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Lineage / genetics Cells, Cultured Conserved Sequence / genetics DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Dopamine / metabolism* Evolution, Molecular Gene Expression Regulation / genetics* Heat-Shock Response Mice Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism Neurogenesis / genetics* Neurons / cytology* Neurons / metabolism* Olfactory Bulb / cytology Olfactory Bulb / metabolism Regulatory Sequences, Nucleic Acid / genetics Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 42.779 |
| 引用数 | 140 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY |
| 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 | F1000Research |
| 各媒体での言及数の合計 | 2 |
| 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 | tm440 tm413 tm801 tm866 tm1734 tm456 tm436 |