Investigating the Role of TCF20 in GABAergic Neurons and its Association with Autism-related Phenotypes in Mouse Models Open Access

Abstract

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders that are marked by deficits in social communications and interactions, repetitive and restrictive patterns of behavior, challenges in learning among many other characteristics and they affect millions of people worldwide. Hundreds of genes linked to ASDs have been identified in efforts to explain the genetic contributions to ASD pathophysiology, with the TCF20 gene getting an increasing amount of attention because of its implication in neurodevelopmental disorders and intellectual disability. Although TCF20 is widely known as a transcription factor that controls gene expression, its exact role in synaptic plasticity, neurodevelopment, and cell-type specific regulation is not understood quite well. GABAergic neurons play an essential role in maintaining the excitatory-inhibitory balance in the brain and are often implicated in the pathophysiology of anxiety and social behavior deficits. In this study, the behavioral and molecular consequences of TCF20 knockout in GABAergic neurons are investigated using conditional knockout mice. Behavioral phenotyping revealed that the TCF20 loss in GABAergic neurons induces anxiety and social avoidance in mice. Immunofluorescent staining demonstrated the selective loss of TCF20 in GABAergic neurons across the cortex, hippocampus, and amygdala. The findings altogether suggest that TCF20 expression in inhibitory neurons plays a part in the regulation of anxiety-related and social behaviors. These insights highlight the significance of cell-type specific transcriptional regulation, elucidate the molecular role of TCF20, and contribute to a broader understanding of ASDs.

Table of Contents

Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Genetics Biology, Molecular
Keyword	TCF20 Neurons Autism GABA Biology ASD Inhibitory
Committee Chair / Thesis Advisor	Jian Zhou, Emory University
Committee Members	David Edwards, Emory University Jitendra Thakur, Emory University

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