Transcriptomic analysis of optic fissure fusion at single cell resolution (RPA-Pilot/Seed Project)

Ocular development is a highly conserved process amongst vertebrates. A critical aspect of assembling of the hemispherical retina from an initially flat sheet of cells requires fusion of the optic fissure (OF). Failure of OF fusion leads to a congenital blinding disorder coloboma. Coloboma is one of the leading causes of pediatric blindness accounting for approximately 10% of cases worldwide. Coloboma presents as a spectrum disorder unilaterally or bilaterally and ranges in severity from minor visual impairment to complete blindness in the affected eye(s). The spectrum of severity is associated with the location and degree to which the OF was able to fuse and the severity of ganglion cell axon loss. We propose to conduct a comprehensive analysis of the transcriptional changes associated with OF fusion. This approach intends to leverage the power of the zebrafish embryo, utility of transgenic lines and advent of the single cell RNA sequencing technology to generate the first highly specific and highly resolved developmental transcriptome of OF fusion. Therefore, we hypothesize that, the combination of a transgenic zebrafish optic fissure reporter line, a detailed time course of samples and scRNA analysis will uncover novel transcriptionally regulated mechanisms mediating optic fissure fusion. Importability, such data would enable our and other labs to systematically assess the molecular contributions of new targets, conservation of their function and begin to draw a more complete picture of OF fusion.