Overview: Most components of signaling pathways involved in the determination of cell fates are conserved across large swaths of the animal phylogeny. Therefore, it is surprising that the activities, modifiers, and ultimate outputs of these pathways vary within and between species.This project will identify and characterize the molecular mechanisms for how conserved signaling pathways are changed and re-wired across diverse individuals in a species to understand this dichotomy. The focus will be on a plastic developmental fate in the nematode Caenorhabditis elegans. This species lives in decaying vegetable matter and eats associated bacteria and fungi. When an environment becomes unfavorable (e.g.. high nematode density, high temperature, or food exhaustion), C. elegans larvae can enter an alternative developmental stage called dauer, a long-lived and stress-resistant dispersal stage. A small number of wild strains have been assayed for the decision to enter dauer, and the trait varies across natural populations. Even though this developmental fate comprises at least four conserved signaling pathways and is well understood in the laboratory strain background, the genes and networks that vary in natural populations to cause differences in the dauer developmental decision are unknown. This proposal seeks to identify the genes that cause these differences and test alternative models for how intraspecific changes in conserved signaling pathways evolve. Intellectual Merit: The C. elegans dauer decision is a powerful model system to understand how a plastic developmental fate varies across natural populations but remains robust enough to ensure species dispersal and survival. In metazoa, few (if any) complex systems are understood at the molecular level in the context of natural populations. To better understand how developmental pathways evolve, this project will leverage C. elegans natural variation in the dauer fate to create a long-standing and tractable system. These discoveries will be made by assaying the production of chemical cues that induce dauer (Obj. 1A) and directly measuring induction of the dauer trait in novel high-throughput assays (Obj. 1B). These approaches will define how signals are produced and received in this developmental fate and identify the genes that vary to cause differences across the C. elegans species. Because these genes and pathways do not act in isolation, dynamic networks of interacting genes (Obj. 2A) will be created and natural variation will be integrated with the inputs, connections, and outputs of these pathways (Obj. 2B). Additionally, the network will incorporate gene expression differences across developmental time and the diversity of the species (Obj. 2C). Each of these approaches will combine to propose a model to understand the evolution of developmental processes in a tractable molecular genetic system with rich species-level resources. Broader Impacts: The impacts of this proposal will have wide-ranging effects on science and society by creating resources to expand access to statistical genetics tools and hands-on lessons about the importance of basic research and evolution for students and the general public. First, the C. elegans Natural Diversity Resource will facilitate quantitative genetics studies by non-expert C. elegans researchers. In this resource, all known C. elegans wild strains are organized and disseminated, all whole-genome sequence and variant data for these strains are publicly released, and tools to perform genome-wide association mappings are provided. Additionall
|Effective start/end date||9/15/18 → 8/31/23|
- National Science Foundation (IOS-1751035-001)
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