The melanocyte lineage in development and disease.
Bottom Line: Melanocyte development provides an excellent model for studying more complex developmental processes.In addition, work on chicken has provided important embryological and molecular insights, whereas studies in zebrafish have allowed live imaging as well as genetic and transgenic approaches.This cross-species approach is powerful and, as we review here, has resulted in a detailed understanding of melanocyte development and differentiation, melanocyte stem cells and the role of the melanocyte lineage in diseases such as melanoma.
Affiliation: MRC Human Genetics Unit and.Show MeSH
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Mentions: The transcription factor microphthalmia-associated transcription factor (MITF) appears to be the master regulator of melanocyte identity and is embedded within a transcriptional network (Fig. 1) that controls the development of melanocytes from the neural crest [reviewed by Baxter et al. (2010)]. Mice lacking MITF cannot form melanocytes (Steingrímsson et al., 2004). Similarly, fish lacking one of the MITF orthologues, mitfa, have no melanocytes, and ectopic expression of mitfa can produce ectopic melanocytes (Lister et al., 1999). Furthermore, the expression of MITF in Medaka embryo-derived stem cells induces differentiation into melanocytes (Béjar et al., 2003), and MITF expression in NIH3T3 cells can activate melanocyte markers (Tachibana et al., 1996). Numerous MITF transcriptional targets have been identified, and include genes encoding components of melanocyte-specific organelles (melanosomes) and the melanin synthesis pathway (see Box 1) as well as more widely expressed genes such as the survival gene Bcl2 (Cheli et al., 2010). In humans, germline mutations in MITF can lead to Waardenburg syndrome or Tietz syndrome [Online Mendelian Inheritance in Man database (OMIM) entries 193510 and 103500, respectively], which are characterised by lack of pigmentation and deafness, as melanocytes also play an important function in the ear. In addition, more subtle changes in MITF transcriptional activity regulated by IRF1 are partially responsible for the pale skin, blue eyes and freckling with brown hair seen in some Northern European populations (Praetorius et al., 2013).Fig. 1.