Decision letter: Gap junctions composed of connexins 41.8 and 39.4 are essential for colour pattern formation in zebrafish

Abstract

The colour patterns that mark an animal's skin, hair, or feathers—called the pigmentation pattern—can be very important for its survival and fitness, helping it to hide from predators or to attract a mate. As a result, there is considerable interest in understanding how genes, proteins, and cells work together to produce the many different pigmentation patterns that exist in the animal world. Adult zebrafish have a characteristic pigmentation pattern of horizontal dark and light stripes on their bodies and fins. There are three types of pigment cell that create this pattern. Xanthophores and iridophores are found all over the body, and the dark stripes also contain melanophore cells. The silvery, reflective iridophores are the first of the cells to populate the skin, giving rise to the first light stripe. They then form a dense network of cells that breaks up to form the darker stripes. However, iridophores are not required to form stripes in the fins, suggesting that patterning occurs differently in the fins and the body. Mutations to a gene called leopard, or leo for short, cause spots to form on the skin of the zebrafish in place of the usual stripes. This gene encodes a member of the connexin family of proteins, which form channels in the membranes that surround cells. These channels—known as gap junctions—allow neighbouring cells to communicate with each other. Each gap junction is made up of two half channels, with one half coming from each neighbouring cells. If the two half channels are identical, the gap junction is known as ‘homomeric’; ‘heteromeric’ gap junctions are made from two different half channels, each consisting of a different connexin protein. The connexin encoded by leo is required for both types of gap junction to form between melanophores and xanthophores. Irion et al. discovered a new mutation to the leo gene that completely disrupts the patterning of the zebrafish. A technique called a genetic screen revealed that the same patterning defects are also seen in the body of zebrafish with mutations to another gene called luchs, which encodes a different connexin protein to the one produced by leo. However, the fins of zebrafish with mutant versions of luchs remain striped. The findings of Irion et al. suggest that heteromeric gap junctions formed from the connexins produced by leo and luchs are important for xanthophores and melanophores to communicate with each other and so form the stripy patterning seen on the body of the zebrafish. The signals transmitted through the gap junctions may also make the iridophores adopt the looser arrangement that is required for the dark stripes to form. As a next step, it will be important to identify the signals that pass through these gap junctions that allow the cells to communicate with their neighbours and establish the pigmentation pattern.