NSF Postdoctoral Fellowship in Biology FY 2021: Defining the role of ZEB2 in the development of convergent neural circuitry for vocal imitation

Gedman, Gregory Louis, New York NY

Investigators

Abstract

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2021, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the Fellow that will contribute to the area of Rules of Life in innovative ways. Vocal imitation is thought to have evolved convergently in songbirds, parrots, and humans because, despite not sharing a common ancestor with this trait, these three groups exhibit similar brain pathways for the production of learned song and speech. The genetic drivers that shape these shared brain pathways and behaviors are not known. Recent cross-species comparisons implicate ZEB2 as a gene important for forming these brain pathways, including that ZEB2 mutations result in impaired speech production in humans. This project aims to understand the role of ZEB2 in the development and function of vocal imitation brain pathways in songbirds and parrots and to relate these findings to humans. Broader impacts include enhancing participation of underrepresented minority students in STEM through a workshop on bioinformatics. In order to test the necessity of ZEB2 for the formation of convergent vocal imitation neural circuitry in songbirds and parrots, the project aims to 1) assess behavioral outcomes following expression manipulation in specific brain regions and 2) define the transcriptomic and chromatin modifications associated with expression manipulation in both species. The Fellow will use RNAi-mediated viral expression vectors to knockdown ZEB2 in songbird HVC (high vocal center) and parrot NLC (central nucleus of the lateral nidopallium), two important premotor analogs shown to control the timing of learned vocalizations in birds. This manipulation will be introduced early in development prior to the formation of the specialized vocal imitation connectivity to test ZEB2’s role in this process. Transcriptomic profiling will be performed to determine the downstream target genes impacted in both species. The Fellow will also profile the regulatory landscape of the ZEB2 transcription factor in both species using ChIP-Seq analysis for chromatin accessibility in these brain regions and adjacent non-vocal imitation regions, highlighting important molecular pathways for vocal imitation. In sum, this project will offer important insights into the constraints on the genome for the convergent evolution of complex behaviors across taxa while offering dozens of new candidate genes for future study. The Fellow will develop expertise in neuroscience, in vivo gene manipulation, and genomic sequencing and will teach a R-based bioinformatics workshop through the RISE program at NMSU. 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.