Defect patterns on the curved surface of fish retinae suggest a mechanism of cone mosaic formation.

Hayden Nunley,Declan A Norton,Rachel O L Wong,Kamirah Martin,Pamela A Raymond,David K Lubensky,Mikiko Nagashima,Alcides Lorenzo Gonzalez,Sachihiro C Suzuki,David Umulis

doi:10.1371/journal.pcbi.1008437

Abstract

The outer epithelial layer of zebrafish retinae contains a crystalline array of cone photoreceptors, called the cone mosaic. As this mosaic grows by mitotic addition of new photoreceptors at the rim of the hemispheric retina, topological defects, called “Y-Junctions”, form to maintain approximately constant cell spacing. The generation of topological defects due to growth on a curved surface is a distinct feature of the cone mosaic not seen in other well-studied biological patterns like the R8 photoreceptor array in the Drosophila compound eye. Since defects can provide insight into cell-cell interactions responsible for pattern formation, here we characterize the arrangement of cones in individual Y-Junction cores as well as the spatial distribution of Y-junctions across entire retinae. We find that for individual Y-junctions, the distribution of cones near the core corresponds closely to structures observed in physical crystals. In addition, Y-Junctions are organized into lines, called grain boundaries, from the retinal center to the periphery. In physical crystals, regardless of the initial distribution of defects, defects can coalesce into grain boundaries via the mobility of individual particles. By imaging in live fish, we demonstrate that grain boundaries in the cone mosaic instead appear during initial mosaic formation, without requiring defect motion. Motivated by this observation, we show that a computational model of repulsive cell-cell interactions generates a mosaic with grain boundaries. In contrast to paradigmatic models of fate specification in mostly motionless cell packings, this finding emphasizes the role of cell motion, guided by cell-cell interactions during differentiation, in forming biological crystals. Such a route to the formation of regular patterns may be especially valuable in situations, like growth on a curved surface, where the resulting long-ranged, elastic, effective interactions between defects can help to group them into grain boundaries.

Highlights

In epithelial sheets that sense an external stimulus, the sensory function often depends on the spatial ordering of the constituent cells
Along ‘rows’, Blue cones alternate with UV cones, and Red cones alternate with Green cones (Fig 1A and 1B)
It is straightforward to demonstrate that a simple row insertion causes a disruption, that is not limited to a point defect but extends along an entire line, in the cone mosaic (Fig 2A)

Summary

Introduction

In epithelial sheets that sense an external stimulus, the sensory function often depends on the spatial ordering of the constituent cells. The precise evolutionary advantage and functional significance of the cone mosaic remain unknown, establishing an organized lattice in which each cone maintains some characteristic spacing from neighboring cones of the same subtype is thought to optimize sensitivity to a broad range of wavelengths over the full spatial extent of the retina [11,12,13]. Four spectral subtypes form the zebrafish cone mosaic: Red, Green, Blue, and Ultraviolet (UV) [14,15]. Blue and UV cones form interpenetrating anisotropic triangular sublattices (Fig 1D). Green and Red cones form interpenetrating anisotropic honeycomb sublattices (Fig 1E). Columns are approximately parallel to the rim of the retina (Fig 1A-1C)

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Conclusion