Unveiling the evolution of neural differentiation mechanisms in animals: a study of the structure and function of the POU-IV/Brn-3 gene regulatory network in Cnidaria.

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Understanding how nervous systems emerged and diversified over evolutionary time is a fundamental problem in biology. This research project will use sea anemones, whose ancestors split off from all other animal lineages over 600 million years ago, to reconstruct the deep evolutionary history of neural development in animals. The resultant knowledge will contribute to the understanding of nervous system evolution in two ways: (1) it will provide fundamental insights into developmental mechanisms that were critical for the origin of nervous systems over 600 million years ago, and 2) it will provide new information about how these mechanisms have diversified in the intervening time period. This project will additionally broaden participation of underrepresented minorities in STEM by actively involving minority undergraduate students directly in research through participation in the Undergraduate Student Mentoring Program of Arkansas INBRE (IDeA Network of Biomedical Research Excellence). Furthermore, the research will strengthen both the research and educational environments at the University of Arkansas by using a unique, non-traditional animal model system that makes it easy give students first-hand experience with cutting-edge biological technologies such as CRISPR-Cas9 genome editing, Next Generation Sequencing, and confocal microscopy. The research will advance fundamental knowledge about the origin and evolution of nervous systems, as well as benefit society through basic science research and education. In bilaterian animals (e.g. mice, worms and flies), the class IV POU homeodomain transcription factor (POU-IV or Brn-3) plays an evolutionarily conserved role in regulating neural subtype differentiation and maintenance. However, it is unclear whether the conservation of POU-IV function extends beyond Bilateria, or whether divergent, novel regulatory mechanisms exist in non-bilaterian animal groups with nervous systems such as Cnidaria (e.g. jellyfish, corals and sea anemones) – the sister group of Bilateria. To address this problem, the research will dissect the structure and function of the POU-IV gene regulatory network in the cnidarian sea anemone Nematostella vectensis. Specifically, this project will focus on 1) defining neural subtypes specified by POU-IV by combining in-depth gene expression analyses with gene function analyses via CRISPR-Cas9-mediated genome editing, and 2) dissecting the structure of the POU-IV gene regulatory network underpinning neural fate specification by combining gene function perturbation, ChIP-seq, and transcriptome analyses.This project is jointly funded by the Organization Program of the Neural Systems Cluster, and the Established Program to Stimulate Competitive Research (EPSCoR).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.