Abstract

Pannexin1 (Panx1) can form ATP-permeable channels that play roles in the physiology of the visual system. In the zebrafish two ohnologs of Panx1, Panx1a and Panx1b, have unique and shared channel properties and tissue expression patterns. Panx1a channels are located in horizontal cells of the outer retina and modulate light decrement detection through an ATP/pH-dependent mechanisms and adenosine/dopamine signaling. Here, we decipher how the strategic localization of Panx1b channels in the inner retina and ganglion cell layer modulates visually evoked motor behavior. We describe a panx1b knockout model generated by TALEN technology. The RNA-seq analysis of 6 days post-fertilization larvae is confirmed by real-time PCR and paired with testing of locomotion behaviors by visual motor and optomotor response tests. We show that the loss of Panx1b channels disrupts the retinal response to an abrupt loss of illumination and it decreases the larval ability to follow leftward direction of locomotion in low light conditions. We concluded that the loss of Panx1b channels compromises the final output of luminance as well as motion detection. The Panx1b protein also emerges as a modulator of the circadian clock system. The disruption of the circadian clock system in mutants suggests that Panx1b could participate in non-image forming processes in the inner retina.

Highlights

  • Pannexin 1 (Panx1) proteins can assemble into two types of integral membrane channels

  • In a previous study we have shown that in the zebrafish retina, Panx1b’s immunoreactivity is prominent in the inner retina and ganglion cells (RGCs) [16], whereas Panx1a is localized on the surface of horizontal cell dendrites invaginating cone pedicles [17]

  • Hind III restriction enzyme recognition sequence located in the spacer region between the transcription activator-like effector nucleases (TALEN) binding sites (Figure 1b)

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Summary

Introduction

Pannexin 1 (Panx1) proteins can assemble into two types of integral membrane channels. It is widely accepted that Panx provide a transmembrane pathway for ATP [1]. Under certain conditions, Panx can act as a highly selective membrane channel for chloride ions without ATP permeability [2]. The cryoEM structure of Panx as a heptameric selective chloride channels was resolved recently [2,3,4,5,6,7,8]. The expression of Panx in the rodent eye has fostered research on functional implications in the normal retina physiology and pathologies related to ocular hypertension or ischemia in mouse models [9,10,11,12,13]. In parallel to ongoing work in rodents, the accessibility of the zebrafish eye at all stages of development to adulthood in combination with the possibility of behavioral assessment of visual system functions allows to study the mechanisms which involve

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