In partial fulfillment of the requirements for the degree of
Doctor of Philosophy in Bioinformatics
in the School of Biological Sciences
George Gruenhagen
Defends his thesis:
Computational analysis of gene expression in the teleost forebrain and the cellular basis of a social behavior
August 8th, 2023
11:00 AM
U.A. Whitaker Building, Room 1214 (UAW 1214)
Zoom Link = https://gatech.zoom.us/j/95008547822
Thesis Advisor:
Dr. J. Todd Streelman
School of Biological Sciences
Georgia Institute of Technology
Committee Members:
Dr. Greg Gibson
School of Biological Sciences
Georgia Institute of Technology
Dr. Joseph Lachance
School of Biological Sciences
Georgia Institute of Technology
Dr. Peng Qiu
Wallace H. Coulter Department of Biomedical Engineering
Georgia Institute of Technology
Dr. Zack Johnson
Department of Psychiatry and Behavioral Sciences
Emory University
Abstract:
Teleosts (ray-finned fish) are the largest vertebrate clade, comprising roughly half of all extant vertebrate species, and can perform complex behaviors requiring advanced cognition. A species of teleost fish, Mchenga conophoros (MC), performs a social behavior called bower-building, whereby males repetitively manipulate sand to form a structure called a bower, over which they court females and chase away competing males. The genetic basis of this social behavior has recently been revealed, but the brain regions and cell populations involved are unknown. Furthermore, the homology of brain regions in the teleost to the mammalian brain is unclear due to the unique folding of the teleost brain during development. This work aims to 1) identify the cellular basis of bower-building in MC and 2) uncover the relationships between cell-types and anatomical regions in the teleost brain to other vertebrates - amphibians, reptiles, birds and mammals.
To address the first aim, we performed single nuclei RNA-sequencing (snRNA-seq) on 19 behaving and 19 paired control male MC, resulting in a total of 33,674 nuclei. We linked genes associated with the evolution of bower-building behavior to a subpopulation of quiescent stem-like cells. We find evidence that behavior-associated neural activity may result in a departure from quiescence and a differential supply of new neurons to a specific region in the teleost brain, the Dl-v.
To determine the relationship of teleostean brain regions, such as the Dl-v, to other vertebrates, we performed spatial transcriptomics, which profiles gene expression within tissue architecture, unlike snRNA-seq. Together, with these complementary technologies, we created a spatially resolved atlas of gene expression in the MC forebrain and compared expression profiles of thousands of genes across vertebrates. We identified ancestral features of non-neuronal and neuronal populations in MC, including hippocampal and surprisingly neocortical populations. The presence of neocortical-like structures in non-mammals is widely debated. Here we find evidence of neocortical transcriptional signatures in the teleost Dl-g. Additionally, we find conserved molecular features of the hippocampus in the teleost Dl-v. In summary, we identified forebrain populations involved in bower-building behavior and ascertained their evolutionary relationships to other vertebrates.