CONICET | Buscador de Institutos y Recursos Humanos

Melanocytes derive from the neural crest cells and arean excellent model to understand the gene expression regulation during celldifferentiation. A gene regulatory network has been reported for zebrafishmelanocyte differentiation. In the network, SRY-boxcontaining gene 10 (sox10) expressionis essential to promote cell differentiation since it activates the master genemicrophthalmia-associated transcriptionfactor a (mitfa).However, sox10 levels need to bereduced because it inhibits the expression of the enzymes responsible formelanin biosynthesis. In mouse and human melanocytes, it is known that Mitf regulates DICER expression; wepropose that sox10 levels are regulated by miRNAs. By RT-qPCR and whole-mountin situ hybridization on zebrafish mutant embryos for dicer1, mitfa, and sox10, we evidenced dicer participation in melanocyte differentiation. Comparing withwild type embryos, dicer1 mutants showedlow levels of melanin, a reduced number of pigment cells, and an aberrantexpression of sox10 during embryodevelopment, while mitfa mutantsshowed low levels of dicer mRNA.Besides, the in silico analysis on dicer1 promoter region revealed thepresence of putative binding sites of Mitfa, and in mitfa and sox10 3?UTRsthe presence of miRNAs binding sites. In order to functional analyse those3?UTRs during melanophore differentiation, experiments in zebrafish embryoswere performed using EGFP as a reporter gene. Results revealed that those3?UTRs were involved in the gene expression regulation. We suggest that dicer1and some miRNAs are involved in controlling sox10and mitfa levels during celldifferentiation. The development of new assays would allow us to incorporate amiRNA family in the gene regulatory network of melanophore differentiation.