Melanosomes in zebrafish RPE Free

The retinal pigment epithelium (RPE) contains numerous melanosomes, but analysis of their formation and function in mammalian models has been hampered by the short time window for melanosome biogenesis in this cell layer. In their study on page 1400, Clare Futter and colleagues take advantage of this timing because it facilitates molecular manipulation using morpholinos, and exploit zebrafish as a model system to genetically dissect melanosome biogenesis in the RPE. Morpholino-mediated knockdown of OA1 greatly reduced the number of melanosomes, but did not affect their size. Next, the authors used 3D electron microscopy to identify two populations of melanosome in the RPE that have similar volumes but are readily distinguishable by their cylindrical or spherical shape. Interestingly, they found that only the cylindrical melanosomes entered the apical processes. The authors then examined the effect of morpholino-mediated knockdown of PMEL, a pigmented-cell-specific protein, on melanosome shape. They found that the formation of cylindrical melanosomes was inhibited, as was their movement into the apical processes, thereby affecting photoreceptor integrity. These findings show that the key mammalian regulators of melanosome biogenesis in the RPE have similar roles in zebrafish, and that PMEL-dependent fibrils generate the cylindrical shape of melanosomes that is required to access the apical processes of the RPE.