Gene expression regulation during melanocyte differentiation: Sox10, Mitfa and Dicer roles

ANDREA M.J. WEINER; ROBERT KELSH; NORA B CALCATERRA

Congreso; LI Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2015

Melanocytes derive from neural crest stem cells and are an excellent model to understand gene expression regulation during cell differentiation. Recently, it was reported a gene regulatory network (GRN) for melanocyte differentiation in zebrafish that elucidated new players, found gene interactions, as well as integrated novel information with previously reported data. In this GRN, sox10 expression is essential for triggering melanocyte differentiation since it activates the master gene mitfa. However, sox10 has to be sharply depleted because it inhibits the expression of enzymes responsible for melanin synthesis. As Mitf regulates Dicer expression in murine and human melanocytes, we speculate that sox10 abundance is controlled by miRNAs. By RT-qPCR and whole mount in situ hybridization on dicer, mitfa and sox10 mutant zebrafish lines we assessed dicer participation in melanocyte differentiation. Comparing to wild-types, dicer mutant showed lower pigmentation and aberrant expression of sox10 while lower abundance of dicer-mRNA was detected in mitfa mutant. Besides, in silico analyses revealed the presence of putative mitfa binding sites in dicer promoter and several predicted miRNA target sites in sox10-3?UTR. All these preliminary results suggest that dicer is involved in the GRN. Further studies will allow us to incorporate a miRNA family in the GRN of melanocyte differentiation.