The Role of Exon Junction Complex Factor RBM8A in Synapse Formation: A Glial Lens
Open Access
- Author:
- Asthana, Shravan
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Yingwei Mao, Thesis Supervisor
Stephen Wade Schaeffer, Thesis Honors Advisor - Keywords:
- Autism Spectrum Disorder
Attention Deficit Hyperactivity Disorder
ASD
ADHD
Neurodevelopmental Disorders
Neurology
Neuroscience
RBM8A
Exon Junction Complex
EJC - Abstract:
- Neurodevelopmental disorders including autism spectrum disorder and attention deficit hyperactivity disorder place a tremendous burden on the patients, families, educational systems, and society at large. While a plethora of neurobiological, genetic, biochemical, neuroimaging, and behavioral studies have greatly increased our breadth and depth of knowledge surrounding the etiology, pathology, and clinical management of such disorders, there are still wide-open questions regarding the underpinnings of such diseases. RNA Binding Motif Protein 8a (RBM8A) - an exon junction complex component - becomes an increasingly important regulator of early gene expression in the central nervous system (CNS) and other tissues. Regulating multiple levels of gene expression, from splicing to translation and mRNA degradation, and influencing dysfunctional human embryonic and neurological development, RBM8A is a clear target for further study into neurodevelopmental disorders. Meanwhile, recent advances in neurobiology clearly evince the astrocyte’s pivotal role in neurodevelopment, and insights into astrocytes in neuropathology is accelerating. Of particular interest is the tripartite synapse, an essential cellular structure where astrocytes could modify signaling and transmission at the molecular, cellular, brain, and even behavioral levels. This thesis presents an investigation into Rbm8a in the mouse astrocyte cell utilizing a conditional knockout model and subsequent behavioral analysis. Results indicate that experimental mice experience significantly increased motor and mobility alongside decreased anxiety, although further morphological and gene expression analysis is necessary to pinpoint the underlying mechanisms. In the context of neurodevelopment, these experiments may describe or further explain the astrocyte’s contribution CNS pathology under Rbm8a deletion, generating more insight via a glial lens of an Rbm8a model of neurodevelopmental disorder.