The evolution of retinoic acid signaling in animals: functional insights from a mollusc embryo

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Retinoic acid is a biologically active version of Vitamin A that acts as a signal between cells and is crucial for human development. Retinoic acid signaling was thought to be a unique characteristic of the vertebrates. Recently however, the genes that control retinoic acid signaling have been found in multiple invertebrate genomes, but it is not clear what retinoic acid signaling is doing in these animals. This project takes advantage of recently discovered roles of retinoic acid signaling in a snail embryo. This group has found that experimental manipulations of several different components of retinoic acid signaling impacted the same structures in the developing embryo, indicating that these different components are working together in a pathway as they do in vertebrates. This project is expected to generate the most comprehensive understanding of retinoic acid signaling outside of vertebrates, and change our understanding of how this pathway arose in evolution. This project will also contribute to the training of undergraduate and graduate level scientists, outreach to local K-12 students, and an open-source teaching resource for undergraduate courses in developmental biology.To characterize the components and roles of the retinoic acid (RA) pathway in the embryo of the gastropod Tritia (aka Ilyanassa), the research team will first use the knowledge of RA effects from preliminary data to carry out a functional screen of 17 additional putative RA pathway component genes, then further test genes with the expected phenotypes for functional interactions with known components. In parallel, they will measure levels of endogenous RA isomers across developmental stages. In a second set of experiments, they will specifically test the effect of RA disruption on the development of the nervous system, a key role of the pathway in vertebrates. A role in neurogenesis has some support from other invertebrates, so this will be an important contribution to that comparative work. These experiments will further the understanding of the roles of RA, and integrate these results with the nascent comparative RA literature. In a final set of experiments, they will test several specific models for the mechanisms of RA function, including whether the system responds to different ligand dosages with different transcription levels.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.