ArticlePLoS genetics2019
Developmental fidelity is imposed by genetically separable RalGEF activities that mediate opposing signals.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Aging, dauer, and stature phenotypes are conferred by structure-directed missense mutations in the endogenous AGE-1/phosphatidylinositol 3-kinase catalytic subunit.bioRxiv : the preprint server for biology · 2026Article
- RAP-2-independent roles formicroPublication biology · 2026Article
- RAP-2 and CNH-MAP4 Kinase MIG-15 confer resistance in bystander epithelium to cell-fate transformation by excess Ras or Notch activity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Functional distinction in oncogenic Ras variant activity in Caenorhabditis elegans.Disease models & mechanisms · 2024Article
- RAL-1 signaling regulates lipid composition inmicroPublication biology · 2024Article
- Identifying the Caenorhabditis elegans vulval transcriptome.G3 (Bethesda, Md.) · 2022Article
- A signalling cascade for Ral.Small GTPases · 2022Review
- Nuclear translocation of the tagged endogenous MAPK MPK-1 denotes a subset of activation events in C. elegans development.Journal of cell science · 2021Article
- Parallel Rap1>RalGEF>Ral and Ras signals sculpt the C. elegans nervous system.Developmental biology · 2021Article
- Ras, Ral, and Rap1 in C. elegans.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Insulated Switches: Dual-Function Protein RalGEFInternational journal of molecular sciences · 2020Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
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.
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