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.