CAREER: Investigating the origins of developmental and regenerative neurogenesis.

Lehigh University, Bethlehem PA

Investigators

Abstract

Understanding the mechanisms that control how embryonic cells become neurons (neurogenesis) is important because nervous systems regulate nearly every aspect of an animal’s life. Many basic aspects of the biology of these cells that would allow scientists to more effectively deal with neural dysfunction and disease is still not understood. The research project will identify the mechanisms of neurogenesis during development and regeneration in a species of sea anemone capable of regenerating its nerve cells, and that is particularly well-suited for state-of-the-art experimental manipulations that would be much more difficult to perform and evaluate in other animals. Because scientists have previously studied a very small number of animal species that undergo development and regeneration, studies in novel animals such as Nematostella are necessary in order to understand the full range of developmental mechanisms that can be used to regulate neurogenesis and promote regeneration, as well as to better understand how alterations to developmental mechanisms contributed to nervous system evolution. The outcomes of this work will improve our fundamental understanding of neurogenesis, and potentially guide future efforts to improve regenerative therapies. The project will also broadly impact STEM students by engaging undergraduates in an advanced lab course where they will conduct cutting-edge research testing hypotheses related to the goals of this project. The focus of the lab is to teach students how to acquire and integrate new knowledge that improves their understanding of scientific questions. The course increases both their scientific literacy and critical reasoning skills, better preparing them for careers in a wide range of STEM fields. This project investigates mechanisms of neuronal induction and neuronal subtype patterning during developmental and regenerative neurogenesis in the cnidarian sea anemone Nematostella. The approach combines gene expression analysis, gene specific functional disruptions, and RNA sequencing to identify mechanisms that neuralize naïve cells and integrate spatial cues to generate specific neuronal subtypes during development and regeneration. The choice of Nematostella as a model is driven in part by the fact that it is one of few animals that allow for direct comparisons between both developmental and regenerative programs in the same species, and that as a cnidarian it will allow researchers to infer the ancestral state from which centralized nervous systems evolved. The results of these studies will enable investigators to begin generating and comparing models of the gene regulatory networks that are responsible for the neurogenesis of specific cell subtypes during both development and regeneration. Additionally, the data set on developmental regulatory networks will allow scientists to better test hypotheses about the origin and evolution of complex centralized nervous systems. The main outcomes of this work will be a more complete view of the degree to which developmental and regenerative neurogenesis overlap, and the first comprehensive data set describing neurogenesis in non-bilaterian animals. 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.