Formation & maintenance of photoreceptor outer segments

Abstract

High-resolution vision is mediated by cone photoreceptors. The molecular programs responsible for the formation and maintenance of their light sensor, the outer segment, are not well understood. In my main project, I correlated daily changes in ultrastructure and gene expression in postmitotic mouse cone photoreceptors in the retina, between birth and eye opening, using serial block-face electron microscopy and RNA sequencing. Outer segments appeared rapidly at postnatal day six and their appearance coincided with a switch in gene expression. The switch affected more than 14\% of all genes expressed in cones. Genes that switched off were rich in transcription factors and neurogenic genes. Those that switched on contained genes relevant for cone function. Extensive chromatin rearrangements in enhancer regions occurred before the switch but not after. This work shows that the growth of a key compartment of a postmitotic sensory cell involves a rapid and extensive switch in gene expression and chromatin accessibility. In a side project, my coworkers and me found that miRNAs 182 and 183 are necessary for cone outer segment maintenance in vivo and functional outer segment formation in stem cell derived retinal organoids.