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Published on: December 22, 2014
Microphthalmia transcription factor induces both retinal pigmented epithelium and neural crest melanocytes from
Nathalie Planque1, Graça Raposo, Laurence Leconte
1UMR 146, Institut Curie Section de Recherche, Bātiment 110, Centre Universitaire, 91405 Orsay Cedex, France.
Abstract:
Mitf encodes a basic helix-loop-helix transcription factor that plays an essential role in the differentiation of the retinal pigmented epithelium (RPE) and neural crest-derived melanocytes. As cells containing melanogenic enzymes (TRP2) are found in Mitf mouse mutants, it is not clear whether Mitf is a downstream factor or a master regulator of melanocyte differentiation. To further study the role of Mitf in committing cells to the melanocyte lineage, we express Mitf in the cultured quail neuroretina cells. This leads to the induction of two types of pigmented cells: neural crest-derived melanocytes, according to their dendritic morphology, physiology, and gene expression pattern are observed together with pigmented epithelial RPE-like cells. The expression of Mitf is lower in pigmented epithelial RPE-like cells than in neural crest-derived melanocytes. Accordingly, overexpression of Mitf in cultured quail RPE causes cells to develop into neural crest-like pigmented cells. Thus, Mitf is sufficient for the proper differentiation of crest-like pigmented cells from retinal cells and its expression level may determine the type of pigment cell induced.
Insights
The microphthalmia-associated transcription factor (Mitf) drives pigment cell differentiation. Its expression level determines whether retinal cells become RPE-like or neural crest-like melanocytes.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Mitf is a transcription factor crucial for retinal pigmented epithelium (RPE) and melanocyte differentiation.
- The precise role of Mitf in melanocyte lineage commitment remains unclear, as some melanogenic enzymes are present in Mitf-deficient cells.
Purpose of the Study:
- To investigate the role of Mitf in cell commitment to the melanocyte lineage.
- To determine if Mitf is a master regulator or downstream factor in pigment cell differentiation.
Main Methods:
- Mitf was expressed in cultured quail neuroretina cells.
- Overexpression of Mitf was performed in cultured quail RPE cells.
- Cell morphology, physiology, and gene expression were analyzed.
Main Results:
- Expression of Mitf in neuroretina cells induced both RPE-like and neural crest-derived melanocytes.
- Mitf expression was lower in RPE-like cells compared to melanocytes.
- Overexpressing Mitf in RPE cells led to neural crest-like pigmented cells.
Conclusions:
- Mitf is sufficient to induce neural crest-like pigmented cells from retinal cells.
- Mitf expression levels can dictate the specific type of pigment cell induced (RPE vs. melanocyte).
- Mitf acts as a key regulator in pigment cell differentiation pathways.
