Oral communication, CS15 / C64

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Mitf mutations promote differentiated cell division and melanoma in zebrafish

The coordination of cell proliferation with differentiation is important for both developmental and cancer biology. In development and in the hair follicle, pigmented melanocytes are thought to be derived from undifferentiated precursor cells or stem cells. However, differentiated melanocytes may also have proliferative capacity in animals, and the potential for differentiated melanocyte cell division in development and regeneration remains largely unexplored. Melanomas often consist of differentiated cells, but little is known about the origin of melanoma cells or how melanoma is maintained. We have used time-lapse imaging of the developing zebrafish to show that while most melanocytes arise from undifferentiated precursor cells, an unexpected subpopulation of differentiated melanocytes arises via cell division. Chemical or genetic depletion of the melanocyte population triggers a regeneration phase in which pigmented melanocyte cell division is significantly enhanced, particularly in young differentiated melanocytes. This process is regulated by Mitf because we find a mitf hypomorphic mutation causes successive differentiated cell divisions in the developing embryo. These results reveal a novel pathway of differentiated melanocyte division that acts in parallel to de novo melanocyte development to rapidly re-establish skin pigmentation in zebrafish. The division potential of differentiated melanocytes may be relevant for stem-cell and differentiation based therapy in melanoma, and in melanocyte regeneration in vitiligo. Mitf mutations have been identified in melanoma and we are now addressing the role of the mutations and differentiated cell division in a zebrafish model of BRAFV600E mitf melanoma.

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