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bioRxiv · 10.1101/381012

Developmental fidelity imposed by the RGL-1 balanced switch mediating opposing signals

Abstract

The six C. elegans vulval precursor cells (VPCs) are induced to form the 30-30-20-{Gamma}-20-3{degrees} 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{degrees} fate and synthesis of DSL ligands. In turn, LIN-12/Notch signal is necessary to induce neighboring cells to become 2{degrees}. 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{degrees} 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{degrees} fate via canonical GEF-dependent activation of RAL-1 and 1{degrees} fate via a non-canonical GEF-independent activity. Our genetic epistasis experiments are consistent with RGL-1 functioning in the modulatory 1{degrees}-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{degrees}- and 2{degrees}-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.

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BibTeXRIS

Shin, H., Braendle, C., Monahan, K. B., Kaplan, R. E. W., Zand, T. P., Mote, F. S., Craig, D. R., Peters, E., Reiner, D. J.. 2018-07-31. Developmental fidelity imposed by the RGL-1 balanced switch mediating opposing signals. https://doi.org/10.1101/381012

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