Defect patterns on the curved surface of fish retinae suggest mechanism of cone mosaic formation
Authors: Nunley Hayden , Nagashima Mikiko , Martin Kamirah , Gonzalez Alcides Lorenzo , Suzuki Sachihiro C. , Norton Declan , Wong Rachel O. L. , Raymond Pamela A. , Lubensky David K. 
Published: October 2019

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 theDrosophilacompound eye. Since defects can provide insight into cell-cell interactions responsible for pattern formation, 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, grain boundaries can form 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 study 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 long-ranged, elastic, effective interactions between defects can help to group them into grain boundaries.

AUTHOR SUMMARY

From hair cells in the mammalian inner ear to the bristles on a fly’s back, sensory cells often form precise arrays, ensuring that these cells are evenly spread out on the tissue’s surface. Here we consider the zebrafish cone mosaic, a crystal of cone photoreceptors in the outer retinal layer. Because the cone mosaic grows from the rim of the curved retinal surface, new rows of cones (i.e., defects) are inserted to maintain constant spacing between sensory cells. We study the spatial distribution of these defects to gain insight into how the cone pattern forms. By imaging retinae in live fish, we find that as differentiating cones are incorporated into the mosaic, defects form lines (grain boundaries) that separate mostly defect-free domains. Then, we show that a computational model based on repulsion between mobile cells during their incorporation into the mosaic generates similar grain boundaries. This study thus suggests that cell motion governed by repulsive cell-cell interactions can play an important role in establishing regular patterns in living systems.