Investigating Expression of Genes Associated with Oculomotor Dysfunction Using Zebrafish

Samantha Hershman*, Alexandra Rose Schmidt, George (AJ) Holmes*, Rebekah Shephard* and Sadie Bergeron, Department of Biology, West Virginia University, Morgantown, WV 26506

Field (Broad Category): Biology (Biological & Biochemical Sciences) 

Student’s Major: Biology 

Oculomotor disruption in schizophrenic patients has been observed by clinicians since the early 1900s. In particular, the anti-saccade (AS) task—which measures one’s ability to refrain from visually tracking irrelevant stimuli— is impaired. Schizophrenia remains one of psychiatry’s most immense challenges, as it is largely untreatable due to its elusive etiology. It is of interest to delineate the genetic factors dictating proper formation and function of the neural circuitry involved with this task in hopes of further understanding the molecular basis of schizophrenia. Two candidate genes, cacng2a and cdh22, were chosen for this project from GWAS studies of anti-saccade error. Both genes have enhancer sites for and are putative target genes of the transcription factor Gsx1. Gsx1 is expressed in the optic tectum in zebrafish and the optic stalk in mice and has roles in glutamatergic neuron differentiation; gsx1 mutant zebrafish lack glutamate transporter expression in the pretectum, indicative of a novel role for gsx1 in visual neural circuit differentiation. In this project, we sought to confirm expression of the AS candidate genes in zebrafish and investigate potential regulation by Gsx1. To achieve this, whole-mount in situ hybridization (WISH) and RTPCR were performed to analyze candidate gene expression at various stages of development. While WISH probe synthesis has been a challenge, preliminary RT-PCR data shows cacng2a expression at specific ages and may lead to the synthesis of an effective probe with which we can assess if and where this gene is expressed with and regulated by gsx1. 

Funding: 

Program/mechanism supporting research/creative efforts: Biology 486 capstone Honors Excel Experiential Grant (2018-2019)