Research Article

Bilateral visual projections exist in non-teleost bony fish and predate the emergence of tetrapods

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Science  09 Apr 2021:
Vol. 372, Issue 6538, pp. 150-156
DOI: 10.1126/science.abe7790

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Dating the ipsilateral visual pathway

In primates, visual connections are bilateral: Each eye sends neural connections to both sides of the brain. Vigouroux et al. looked at the evolutionary underpinnings of the bilateral visual system. A close look at the connections between the retina and the brain in a variety of fish species representing a span of evolutionary divergence revealed that contralateral connections seem to be universal. The ipsilateral connections, which add to the contralateral connections to form a bilateral visual system, arrived later in evolution but before the transition to land-dwelling animals.

Science, this issue p. 150

Structured Abstract

INTRODUCTION

Depth perception [stereoscopic or three-dimensional (3D) vision] exists in vertebrate and nonvertebrate species and has been linked to binocularity, the partial overlap of the visual fields, and to disparities of the images coming from both eyes. In mammals, the right and left sides of the brain receive visual inputs from both eyes and compute their differences to extract 3D visual information. Mammals with front-facing eyes, such as primates and carnivores, possess a high fraction of ipsilateral fibers and therefore a higher degree of binocular overlap, whereas lateral-eyed prey mammals have a small amount of ipsilateral retinal axons and a more limited binocular overlap. This prevalent model also assumes that ipsilateral projections evolved within amphibians first and were absent in fishes. However, isolated and often conflicting data reported the presence of ipsilateral retina connections in fishes, without any clear correlation with eye position or predatory behavior.

RATIONALE

We decided to systematically investigate the presence of ipsilateral and contralateral visual projections in a panel of teleost and non-teleost fishes by using advanced histological methods and whole-mount brain imaging. We sampled a large spectrum of fish species, varying for eye position, predatory behavior, and evolutionary history. We further evaluated in fishes the level of conservation of the genetic program that, in mammals, is thought to specify ipsilateral visual projections.

RESULTS

By injecting fluorescent axonal tracers in the eyes of 11 fish species and imaging their brains after optical clearing, we analyzed their patterns or retinal connectivities at high resolution. Only contralateral projections were found in most teleost fishes. However ipsilateral projections were present in the most basally branching teleost fish and in non-teleosts. In the non-teleost spotted gar, we detected a proportion of ipsilateral fibers comparable to what was previously reported in rodents. The presence of ipsilateral connections did not correlate with eye position or the life history of the individual species. Ipsilateral visual projections were also present in lungfish, the closest living fish relative of tetrapods, including mammals. In mammals, the genetic program driving ipsilateral retina connectivity is initiated by the transcription factor Zic2. We analyzed ZIC2 expression in humans and showed that it is expressed in the temporal retina quadrant where ipsilateral projecting cells are located. By contrast, no Zic2 expression was detected in the spotted gar retina, despite the substantial proportion of ipsilateral projection in this species. Zic2 is also absent in retinal neurons of zebrafish, a teleost with only contralateral visual projections. However, we showed that ectopically expressing Zic2 in the zebrafish retina could induce the formation of ipsilateral connections.

CONCLUSION

Our data reveal that ipsilateral retina projections are a widespread feature in the fish visual system, with many species having a proportion of ipsilateral projections comparable to those in several mammals. Unlike in mammals, the presence of ipsilateral projections in fish does not correlate with animal life history or eye position in the head, but rather with phylogenetic position in the piscine tree of life. Ipsilateral visual projections are present in all non-teleost fish branches and thus were likely ancestral and then lost in modern teleosts. Because we further detected ipsilateral projections in the lungfish, a close relative to tetrapods, we propose that ipsilateral projections were present already in the last common ancestor of bony vertebrates. Although Zic2 is dispensable for ipsilaterally projecting cell specification in the gar retina, it is able to reactivate a genetic program that specifies the formation of these cells in zebrafish, where they are normally not present, further supporting deep homology of this trait among both aquatic and terrestrial bony vertebrates.

Evolution history of visual system bilaterality.

(Top) Simplified phylogenetic tree of vertebrates. Most teleost lineages lack ipsilateral visual projections, but in the most basally branching ray-finned fish and in lobe-finned fish, eyes project to both the ipsilateral and contralateral sides of the brain, as in tetrapods. (Bottom) Schematic drawings of visual system connectivity in a teleost, two non-teleosts (gar and lungfish), and a tetrapod. Left and right retinal projections are shown in orange and blue, respectively.

Abstract

In most vertebrates, camera-style eyes contain retinal ganglion cell neurons that project to visual centers on both sides of the brain. However, in fish, ganglion cells were thought to innervate only the contralateral side, suggesting that bilateral visual projections appeared in tetrapods. Here we show that bilateral visual projections exist in non-teleost fishes and that the appearance of ipsilateral projections does not correlate with terrestrial transition or predatory behavior. We also report that the developmental program that specifies visual system laterality differs between fishes and mammals, as the Zic2 transcription factor, which specifies ipsilateral retinal ganglion cells in tetrapods, appears to be absent from fish ganglion cells. However, overexpression of human ZIC2 induces ipsilateral visual projections in zebrafish. Therefore, the existence of bilateral visual projections likely preceded the emergence of binocular vision in tetrapods.

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