Developmental fidelity imposed by the RGL-1 Balanced Switch mediating opposing signals Institutional Repository Document uri icon


  • AbstractThe sixC. elegansvulval precursor cells (VPCs) are induced to form the 30-30-20--20-3 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. In turn, LIN-12/Notch signal is necessary to induce neighboring cells to become 2. We previously showed that, in response to lower dose of 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 functions. 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 developmentally 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 and 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 without 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 as a Balanced Switch that orchestrates opposing 1- and 2-promoting modulatory cascades to decrease inappropriate fate decisions. We speculate that such switches are broadly conserved but mostly masked by paralog redundancy or essential genes.

altmetric score

  • 1.5

author list (cited authors)

  • Shin, H., Braendle, C., Monahan, K. B., Kaplan, R., Zand, T. P., Mote, F. S., ... Reiner, D. J.

citation count

  • 0

complete list of authors

  • Shin, Hanna||Braendle, Christian||Monahan, Kimberly B||Kaplan, Rebecca EW||Zand, Tanya P||Mote, F Sefakor||Craig, DeSean R||Peters, Eldon||Reiner, David J

Book Title

  • bioRxiv

publication date

  • July 2018