Author ORCID Identifier

https://orcid.org/0009-0002-9618-5689

Semester

Spring

Date of Graduation

2026

Document Type

Thesis (Campus Access)

Degree Type

MS

College

Eberly College of Arts and Sciences

Department

Biology

Committee Chair

Sadie Bergeron

Committee Member

Eric Horstick

Committee Member

Martin Hruska

Abstract

During vertebrate neurodevelopment, transcription factors regulate gene expression programs that guide neuronal differentiation and circuit formation to generate the cellular diversity required for a functional nervous system. Disruption of these regulatory networks can alter neuronal identity and impair neural circuit development. Gene mutation studies in model organisms provide a powerful approach for identifying roles of transcription factors. In this thesis, I investigated the previously uncharacterized roles of the transcription factor Genomic screen homeobox 1 (Gsx1) in visually mediated behaviors and catecholaminergic neuron differentiation.

In Chapter 2, I examined the effects of a presumed gsx1 loss-of-function mutation on catecholaminergic neuron populations by analyzing the expression of Tyrosine hydroxylase 1 (Th1), a rate limiting enzyme required for the synthesis of dopamine, norepinephrine, and epinephrine. Using immunohistochemistry, I assessed Th1 expression across several regions in the central nervous system (CNS) which include the olfactory bulb (OB), subpalium (S), caudal hindbrain (cHb), preoptic area (Po), and medial and lateral pretectum (mPr and lPr).  Significant findings include a reduction in Th1 expression in the mPr and a small cluster of neurons in the cHb in gsx1mutants (gsx1y689), indicating a region-specific requirement for gsx1 in the differentiation or maintenance of dopaminergic and noradrenergic neurons. These findings add to previous work demonstrating that gsx1 regulates neuronal differentiation, and they identify dopaminergic and noradrenergic neurons as additional neuronal subtypes influenced by gsx1 expression, beyond the previously characterized glutamatergic populations.

In Chapter 3, I further investigate the functional consequences of the presumed loss of function of gsx1 by evaluating additional visually mediated behaviors in gsx1y689 larvae. First, I assessed light-mediated turn bias behavior, which requires visual circuits that form between the retina and the thalamus. Mutant larvae displayed normal light mediated turning behavior, consistent with this circuitry remaining morphologically intact. To examine more complex visuomotor processing in gsx1y689, I then analyzed the optokinetic response (OKR), a reflexive eye movement that tracks the direction of the visual stimulus followed by a fast reset. Although gsx1y689 generated OKR, they exhibited a reduction in the number of saccades during tracking, suggesting impaired visual motion processing. This result is consistent with the morphological disruption of retina to optic tectum neural circuits that are required for visual information integration in gsx1y689.

Collectively, the findings presented in this thesis demonstrate that gsx1 plays additional previously unidentified roles in neuronal differentiation and functional circuit development within the zebrafish CNS. Specifically, gsx1 contributes to the development of dopaminergic neurons in the mPr, a small cluster of noradrenergic neurons in the caudal hindbrain, and the visually mediated behavior OKR but not the light mediated turn behavior. Notably, Gsx1 selectively regulates and refines specific neural circuits rather than broadly regulating circuit development.

Download

Share

COinS