論文 - 詳細
| RRC ID | 59596 |
|---|---|
| 著者 | Shin H, Braendle C, Monahan KB, Kaplan REW, Zand TP, Mote FS, Peters EC, Reiner DJ. |
| タイトル | Developmental fidelity is imposed by genetically separable RalGEF activities that mediate opposing signals. |
| ジャーナル | PLoS Genet |
| Abstract |
The six C. elegans vulval precursor cells (VPCs) are induced to form the 3°-3°-2°-1°-2°-3° pattern of cell fates with high fidelity. In response to EGF signal, the LET-60/Ras-LIN-45/Raf-MEK-2/MEK-MPK-1/ERK canonical MAP kinase cascade is necessary to induce 1° fate and synthesis of DSL ligands for the lateral Notch signal. In turn, LIN-12/Notch receptor is necessary to induce neighboring cells to become 2°. We previously showed that, in response to graded EGF signal, the modulatory LET-60/Ras-RGL-1/RalGEF-RAL-1/Ral signal promotes 2° fate in support of LIN-12. In this study, we identify two key differences between RGL-1 and RAL-1. First, deletion of RGL-1 confers no overt developmental defects, while previous studies showed RAL-1 to be essential for viability and fertility. From this observation, we hypothesize that the essential functions of RAL-1 are independent of upstream activation. Second, RGL-1 plays opposing and genetically separable roles in VPC fate patterning. RGL-1 promotes 2° fate via canonical GEF-dependent activation of RAL-1. Conversely, RGL-1 promotes 1° fate via a non-canonical GEF-independent activity. Our genetic epistasis experiments are consistent with RGL-1 functioning in the modulatory 1°-promoting AGE-1/PI3-Kinase-PDK-1-AKT-1 cascade. Additionally, animals lacking RGL-1 experience 15-fold higher rates of VPC patterning errors compared to the wild type. Yet VPC patterning in RGL-1 deletion mutants is not more sensitive to environmental perturbations. We propose that RGL-1 functions to orchestrate opposing 1°- and 2°-promoting modulatory cascades to decrease developmental stochasticity. We speculate that such switches are broadly conserved but mostly masked by paralog redundancy or essential functions. |
| 巻・号 | 15(5) |
| ページ | e1008056 |
| 公開日 | 2019-5-1 |
| DOI | 10.1371/journal.pgen.1008056 |
| PII | PGENETICS-D-18-01808 |
| PMID | 31086367 |
| PMC | PMC6534338 |
| MeSH | Animals Body Patterning / genetics Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Epidermal Growth Factor / genetics* Epidermal Growth Factor / metabolism Epistasis, Genetic Female Fertility / genetics Gene Expression Regulation, Developmental* Guanine Nucleotide Exchange Factors / genetics* Guanine Nucleotide Exchange Factors / metabolism Receptors, Notch / genetics Receptors, Notch / metabolism Signal Transduction Stem Cells / cytology Stem Cells / metabolism Vulva / cytology Vulva / growth & development Vulva / metabolism* raf Kinases / genetics raf Kinases / metabolism ral GTP-Binding Proteins / genetics ral GTP-Binding Proteins / metabolism ras Proteins / genetics ras Proteins / metabolism |
| IF | 5.224 |
| 引用数 | 0 |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 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 | tm2760 tm5205 tm2255 tm6137 |