論文 - 詳細
| RRC ID | 59443 |
|---|---|
| 著者 | Attner MA, Keil W, Benavidez JM, Greenwald I. |
| タイトル | HLH-2/E2A Expression Links Stochastic and Deterministic Elements of a Cell Fate Decision during C. elegans Gonadogenesis. |
| ジャーナル | Curr Biol |
| Abstract |
Stochastic mechanisms diversify cell fate in organisms ranging from bacteria to humans [1-4]. In the anchor cell/ventral uterine precursor cell (AC/VU) fate decision during C. elegans gonadogenesis, two "α cells," each with equal potential to be an AC or a VU, interact via LIN-12/Notch and its ligand LAG-2/DSL [5, 6]. This LIN-12/Notch-mediated interaction engages feedback mechanisms that amplify a stochastic initial difference between the two α cells, ensuring that the cell with higher lin-12 activity becomes the VU while the other becomes the AC [7-9]. The initial difference between the α cells was originally envisaged as a random imbalance from "noise" in lin-12 expression/activity [6]. However, subsequent evidence that the relative birth order of the α cells biases their fates suggested other factors may be operating [7]. Here, we investigate the nature of the initial difference using high-throughput lineage analysis [10]; GFP-tagged endogenous LIN-12, LAG-2, and HLH-2, a conserved transcription factor that orchestrates AC/VU development [7, 11]; and tissue-specific hlh-2 null alleles. We identify two stochastic elements: relative birth order, which largely originates at the beginning of the somatic gonad lineage three generations earlier, and onset of HLH-2 expression, such that the α cell whose parent expressed HLH-2 first is biased toward the VU fate. We find that these elements are interrelated, because initiation of HLH-2 expression is linked to the birth of the parent cell. Finally, we provide a potential deterministic mechanism for the HLH-2 expression bias by showing that hlh-2 is required for LIN-12 expression in the α cells. |
| 巻・号 | 29(18) |
| ページ | 3094-3100.e4 |
| 公開日 | 2019-9-23 |
| DOI | 10.1016/j.cub.2019.07.062 |
| PII | S0960-9822(19)30942-X |
| PMID | 31402303 |
| PMC | PMC6759384 |
| MeSH | Animals Basic Helix-Loop-Helix Transcription Factors / biosynthesis Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism* Caenorhabditis elegans Caenorhabditis elegans Proteins / biosynthesis Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Differentiation / physiology Cell Lineage Genes, Reporter Gonads / cytology Gonads / growth & development* Gonads / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism Organogenesis Receptors, Notch / genetics Receptors, Notch / metabolism Sex Differentiation Signal Transduction Transcription, Genetic |
| IF | 9.193 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 27 |
| 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 | |