Transcriptional and post-translational regulation of MITF-M expression and activity

Melanocytes, neurons and glia all arise from precursor cells derived from neural crest cells. Cells that will give rise to neurons and glia migrate away from the neural crest earlier and in a ventral pattern, while cells that will give rise to melanocytes leave the neural crest later and migrate dorsolaterally. Nevertheless, melanocytes can also arise in an alternate pathway from dual Schwann cell/melanocyte precursors or by dedifferentiation from Schwann cells, a derivative of the glial lineage (reviewed in Mort et al, 2015). MITF-M is a key regulator of melanocyte development, and its expression distinguishes the melanocyte fate from that of glial and neural cells. MITF-M expression is repressed in precursors through the activity of FOXD3 and SOX2. Depending on the species, these transcription factors may either bind directly to elements in the MITF-M promoter to repress transcription, or may act independently of DNA binding by disrupting protein-protein interactions that promote transcriptional activity (Nitzan et al, 2013a,b; Curran et al, 2009, 2010; Adameyko et al, 2012; reviewed in Mort et al, 2015; White and Zon, 2008; Goding and Arnheiter, 2019). FOXD3 and SOX2 expression, in turn, are regulated by a cascade of other transcription factors, including ZIC1, PAX3, SNAIL2 and SOX9 (reviewed in Mort et al, 2015; Goding and Arnheiter, 2019).

Summary from Reactome (R-HSA-9856649), read 2026-09-23.