CONICET | Buscador de Institutos y Recursos Humanos

Melanocytes derive from neural crest cells and aregenetically well characterised, making them an excellent model forunderstanding how regulation of gene expression enables cell differentiation. Acore gene regulatory network (GRN) has been reported for zebrafish melanocytedifferentiation. In this network, the expression of SRY-box containing gene 10(sox10) is essential to promote celldifferentiation since it activates the master gene microphthalmia-associatedtranscription factor a (mitfa).However, sox10 levels needsubsequently to be reduced because it inhibits the expression of the enzymesresponsible for melanin biosynthesis. In mouse and human Mitf regulates DICERexpression, leading us to hypothesise that miRNA expression contributes todown-regulation of sox10. UsingRT-qPCR and whole-mount in situhybridization on zebrafish embryos mutant for dicer1, mitfa, and sox10, we demonstrated the participation ofdicer1 in melanocyte differentiation. Zebrafish dicer1 mutants showed low levels of melanin, a reduced number ofpigment cells, and an aberrant expression of sox10 during embryo development, while mitfa mutants showed low levels of dicer1 mRNA. Furthermore, insilico analysis of the dicer1promoter region revealed the presence of putative binding sites for Mitfa, andthe presence of complementary miRNAs seed-regions in both mitfa and sox10 3?UTRs.EGFP reporter gene experiments showed the functional relevance of these 3?UTRsin melanophore differentiation in zebrafish embryos. We suggest that dicer1 and some miRNAs are importantcomponents of the melanocyte GRN, controlling sox10 and mitfa levelsduring cell differentiation.