The formation of the light-sensing compartment of cone photoreceptors coincides with a transcriptional switch.

Janine M Daum,Michael Stadler,Botond Roska,Filippo M Rijli,Özkan Keles,Sjoerd Jb Holwerda,Hubertus Kohler

doi:10.7554/elife.31437

Abstract

High-resolution daylight vision is mediated by cone photoreceptors. The molecular program responsible for the formation of their light sensor, the outer segment, is not well understood. We correlated daily changes in ultrastructure and gene expression in postmitotic mouse cones, between birth and eye opening, using serial block-face electron microscopy (EM) and RNA sequencing. Outer segments appeared rapidly at postnatal day six and their appearance coincided with a switch in gene expression. The switch affected over 14% of all expressed genes. Genes that switched off were rich in transcription factors and neurogenic genes. Those that switched on contained genes relevant for cone function. Chromatin rearrangements in enhancer regions occurred before the switch was completed, but not after. We provide a resource comprised of correlated EM, RNAseq, and ATACseq data, showing that the growth of a key compartment of a postmitotic cell involves an extensive switch in gene expression and chromatin accessibility.

Highlights

The nervous system extracts information from the environment via specialized sensory cells, which convert changes in physical quantities such as the number of photons, mechanical pressure, or the concentration of chemicals into neuronal signals
We analyzed ten different time points from postnatal day 0 (P0) to P11 by 3D reconstructing the ultrastructure of the photoreceptor layer using serial block-face electron microscopy (Busskamp et al, 2014a; Denk and Horstmann, 2004)
Outer segments were absent until P4, their number abruptly increased from 7% of the cells having an outer segment at P5 to 53% at P6, and continued to increase until P11 (Figure 1, Figure 1—figure supplement 1)

Summary

Introduction

The nervous system extracts information from the environment via specialized sensory cells, which convert changes in physical quantities such as the number of photons, mechanical pressure, or the concentration of chemicals into neuronal signals. This conversion takes place in primary ciliumderived, dedicated neuronal compartments (Avidor-Reiss et al, 2004). Concentration of chemicals is detected in the cilia of the olfactory receptor neurons in the olfactory system. These different, antenna-like, modified cilia are especially sensitive to genetic perturbations and are the most frequent sites of sensory loss (Mitchison and Valente, 2017; Wheway et al, 2014)

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Conclusion