Melanophore Migration and Survival during Zebrafish Adult Pigment Stripe Development Require the Immunoglobulin Superfamily Adhesion Molecule Igsf11

Abstract

The zebrafish adult pigment pattern has emerged as a useful model for understanding the development and evolution of adult form as well as pattern-forming mechanisms more generally. In this species, a series of horizontal melanophore stripes arises during the larval-to-adult transformation, but the genetic and cellular bases for stripe formation remain largely unknown. Here, we show that the seurat mutant phenotype, consisting of an irregular spotted pattern, arises from lesions in the gene encoding Immunoglobulin superfamily member 11 (Igsf11). We find that Igsf11 is expressed by melanophores and their precursors, and we demonstrate by cell transplantation and genetic rescue that igsf11 functions autonomously to this lineage in promoting adult stripe development. Further analyses of cell behaviors in vitro, in vivo, and in explant cultures ex vivo demonstrate that Igsf11 mediates adhesive interactions and that mutants for igsf11 exhibit defects in both the migration and survival of melanophores and their precursors. These findings identify the first in vivo requirements for igsf11 as well as the first instance of an immunoglobulin superfamily member functioning in pigment cell development and patterning. Our results provide new insights into adult pigment pattern morphogenesis and how cellular interactions mediate pattern formation.

Author Summary

Vertebrate pigment patterns are stunningly diverse and have been an important model of pattern formation for more than a century. Nevertheless, we still know remarkably little about the genes and cell behaviors that underlie the generation of specific patterns. To elucidate such mechanisms, a large number of pigment pattern mutants have been isolated in the genetically tractable zebrafish. Instead of the normal horizontal stripe pattern, many of these mutants exhibit spots of varying sizes and degrees of organization. Here, we show that one such mutant, seurat, named for the 19th century pointillist, George Seurat, exhibits lesions in the gene encoding a classical cell adhesion molecule (CAM) of the immunoglobulin superfamily, Igsf11. We find that Igsf11 mediates cell adhesion and promotes the migration and survival of melanophores and their precursors during adult stripe formation. These results are exciting because they are the first time that a CAM has been implicated in pigment pattern formation, despite the long-standing expectation that such molecules might be required to regulate adhesive interactions during these events. These cellular phenotypes further represent the first known in vivo functions for Igsf11 and point to the potential for similar activities amongst the rich diversity of immunoglobulin superfamily members.