In partial fulfillment of the requirements for the degree of
Doctor of Philosophy in Biology
In the
School of Biological Sciences
Sydney Popsuj
Will defend her dissertation
Regulation of Motor Neuron Differentiation in the Tunicate Larva
APRIL 23, 2025
10-11AM
HOWEY L3
https://gatech.zoom.us/my/albertostolfi?pwd=WjQyZXVvd1B0V0NUNTFsUnZKUlN3Zz09
Thesis Advisor:
Alberto Stolfi, Ph.D.
School of Biological Sciences
Georgia Institute of Technology
Committee Members:
Shuyi Nie, Ph.D.
School of Biological Sciences
Georgia Institute of Technology
Joseph Lachance, Ph.D.
School of Biological Sciences
Georgia Institute of Technology
Patrick McGrath, Ph.D.
School of Biological Sciences
Georgia Institute of Technology
Billie Swalla, Ph.D.
Department of Biology
University of Washington
Dissertation Summary: In this work, I investigate the gene regulatory networks responsible for the differentiation of unique neuron subtypes in the Ciona larval motor ganglion (MG), which functions as the organism’s central pattern generator (CPG) with specific interest in the motor neurons. I demonstrate transcription factor Ebf, is a terminal selector for cholinergic fate in a single dorsal hindbrain interneuron, Ascending Motor Ganglion Neuron 5 (AMG5), yet does not work as a terminal selector in the “core” MG, where the primary motor neurons reside. To further understand the regulation of cholinergic fate in the core MG, I tested the roles of conserved, motor neuron-enriched transcription factors Onecut, Neurogenin, and Lhx3/4. I also identified a crucial role for Ebf in the regulation of a deeply conserved pathway governing the alternative splicing of Agrin for neuromuscular junction formation, which we also describe for the first time in a non-vertebrate organism. Finally, I investigated the regulation of the specialized neuromuscular synapses formed by the Motor Neuron 1 (MN1) pair of neurons, which are primarily responsible for locomotion in Ciona larvae. More specifically, I revealed a role for the transcription factor Nkx6 in specifying MN1, and showed that the conserved Wnt pathway inhibitor Dkk3 is also required for MN1 neuromuscular synapse formation. My work provides key insights into the development and evolution of cholinergic neurons involved in chordate locomotion.