Transcriptomic analyses link changes in gene expression to defects in pigment cell differentiation and eye...

The oculocutaneous albinism 2 protein is required for melanin synthesis in vertebrates and its loss of function leads to one of the most common forms of skin and eye albinism, Oculocutaneous albinism (OCA). Using a zebrafish disease model for OCA2, we explore developmental explanations for pleiotropic traits observed in humans with OCA2. At multiple stages, we find that oca2 mutant zebrafish exhibit abnormal number and location of iridophores, an accessory pigment cell type that arises from neural crest cells in fish and amphibians. In addition, oca2 mutants display defects during eye development including delayed choroid fissure closure and significant changes in retinal cell differentiation and organization. Our transcriptomic analysis of oca2 mutants revealed alterations in gene networks involved in differentiation of neural crest cells, retinal neurons, and the retinal pigment epithelium (RPE) including Notch and Wnt/β-catenin pathway genes. Together, our data provide information about developmental consequences of oca2 mutation and support the possibility that the Oca2 protein may function in neural crest differentiation and eye development.