Abstract
Purpose :
Developmental eye disorders such as microphthalmia affect roughly 1 in every 7,000 live births. Nearly 20% of these cases are due to a mutation in the proliferative gene, sox2. While transcriptional control of sox2 is well understood, the mechanisms for its post-transcriptional control have not been addressed. Our preliminary data has found the RNA binding protein, rbm24a, regulates sox2. The purpose of our study is to determine the cellular mechanism underlying the microphthalmia phenotype and identify additional RNA targets of rbm24a.
Methods :
We use gene knockdown and CRISPR genome editing to reduce rbm24a in zebrafish. We characterize developmental defects, evaluate predicted targets by qPCR, and perform behavioral studies to assess visual acuity.
Results :
Knockdown and somatic CRISPR mutation of rbm24a leads to microphthalmia. We find that knockdown of rbm24a leads to a 70% decrease in sox2 expression. Using the vision startle response with software developed in our lab, we show rbm24a morphants are able to detect stark changes in light. However, rbm24a deficient embryos are unable to follow a sinusoidal pattern, suggesting a subtle defect in vision or a defect in visual processing.
Conclusions :
Our study highlights a novel mechanism for rbm24a in the post-transcriptional regulation of sox2. Additionally, this work demonstrates the usefulness of the zebrafish as a model for visual function studies.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.