Developmental fidelity is imposed by genetically separable RalGEF activities that mediate opposing signals.

作者: Hanna Shin , Christian Braendle , Kimberly B. Monahan , Rebecca E. W. Kaplan , Tanya P. Zand

DOI: 10.1371/JOURNAL.PGEN.1008056

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摘要: 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 EGF signal, LET-60/Ras-LIN-45/Raf-MEK-2/MEK-MPK-1/ERK canonical MAP kinase cascade is necessary induce 1° fate and synthesis DSL ligands for lateral Notch signal. turn, LIN-12/Notch receptor neighboring become 2°. We previously showed that, in graded modulatory LET-60/Ras-RGL-1/RalGEF-RAL-1/Ral signal promotes 2° support LIN-12. this study, we identify two key differences between RGL-1 RAL-1. First, deletion confers no overt developmental defects, while previous studies RAL-1 be essential viability fertility. From observation, hypothesize that functions independent upstream activation. Second, plays opposing genetically separable roles VPC patterning. via GEF-dependent activation Conversely, a non-canonical GEF-independent activity. Our genetic epistasis experiments consistent functioning 1°-promoting AGE-1/PI3-Kinase-PDK-1-AKT-1 cascade. Additionally, animals lacking experience 15-fold higher rates patterning errors compared wild type. Yet mutants not more sensitive environmental perturbations. propose orchestrate 1°- 2°-promoting cascades decrease stochasticity. speculate such switches broadly conserved but mostly masked by paralog redundancy or functions.

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