Exploring the Role of RNA-Binding Protein GIGYF2 in Development

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Restricted (Penn State Only)
Author:
Tong, Mabel
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Yingwei Mao, Thesis Supervisor
Timothy J Jegla, Thesis Honors Advisor
Keywords:
Autism Spectrum Disorder
ASD
Neurodevelopmental Disorders
Neuroscience
GIGYF2
Abstract:
Autism spectrum disorders fall under the umbrella of neurodevelopmental disorders that have received increasing attention in recent years due to scientific advancements, increased awareness, and rising prevalences. Technological advancements in the field of neuroscience, imaging, genetics, and behavioral studies attempt to provide a more holistic picture of diseases and disorders such as ASDs. However, there remain research gaps in connecting ASD from childhood into adulthood as well as understanding rare de novo mutations and the impact on phenotypic and pathological outcomes. This thesis aims to investigate the role of Gigyf2, identified by prior literature as an interest risk gene for ASD, in neurodevelopment. Based on Gigyf2’s known involvement in the 4EHP-GIGYF2 translation repression complex and IGF-1 pathway, the hypothesis was that knockout mice would have increased neuronal stem cell density and mitosis in staining results as well as increased cranium measurements as associated with ASD macrocephaly. The hypothesis was tested by collecting and analyzing prenatal E15 and postnatal P60 mice samples for slicing, staining, imaging, cell counting, and microcomputed tomography scanning. A statistically significant increase in neural stem cell density was observed in heterozygous E15 mutants with increased nasal bone length in male P60 heterozygous mice and decreased frontal bone width in female P60 heterozygous mice compared to wild type. The increase in neural stem cells and cranium measurements suggest that Gigyf2 does play a role in impaired neurodevelopment that remains to be further explored in the context of ASD and the previously identified de novo mutations in the gene.