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T Burgoyne, MN O'Connor, MC Seabra, DF Cutler and CE Futter
Abstract
Analysis of melanosome biogenesis in the retinal pigment epithelium (RPE) is challenging because it occurs predominantly in a short embryonic time window. Here we show that the zebrafish provides an ideal model system for studying this process because in the RPE the timing of melanosome biogenesis facilitates molecular manipulation using morpholinos. Morpholino-mediated knockdown of OA1, mutations in which cause the most common form of human ocular albinism, induces a major reduction in melanosome number, recapitulating a key feature of the mammalian disease where reduced melanosome numbers precede macromelanosome formation. We further show that PMEL, a key component of mammalian melanosome biogenesis, is required for generation of cylindrical melanosomes in zebrafish, in turn required for melanosome movement into the apical processes and maintenance of photoreceptor integrity. Spherical and cylindrical melanosomes containing similar melanin volumes co-exist in the cell body but only cylindrical melanosomes enter the apical processes. Taken together our findings indicate that melanosome number and shape are independently regulated and that melanosome shape controls a function in the RPE that depends on localization in the apical processes.
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Concepts
Melanocyte, Melanism, Ocular albinism, Melanosome, Retinal pigment epithelium, Albinism, Retina, Melanin
MeSH headings
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