Genetics of pigment cells: lessons from the tyrosinase gene family.

ISREC (Swiss Institute for Experimental Cancer Research), National Center of Competence in Research Molecular Oncology, Epalinges, Switzerland.
Histology and histopathology (Impact Factor: 2.24). 06/2006; 21(5):567-78.
Source: PubMed

ABSTRACT In mammals, the melanin pigment is produced in two cell types of distinct developmental origins. The melanocytes of the skin originate form the neural crest whereas the retinal pigment epithelium (RPE) of the eye originates from the optic cup. The genetic programs governing these two cell types are thus quite different but have evolved to allow the expression of pigment cell-specific genes such as the three members of the tyrosinase-related family. Tyrosinase, Tyrp1 and Dct promoters contain a motif termed E-box which is bound by the transcription factor Mitf. These E-boxes are also found in the promoters of the corresponding fish genes, thus highlighting the pivotal role of Mitf in pigment cell-specific gene regulation. Mitf, which displays cell type-specific isoforms, transactivates the promoters of the tyrosinase gene family in both pigment cell lineages. However, specific DNA motifs have been found in these promoters, and they correspond to binding sites for RPE-specific factors such as Otx2 or for melanocyte-specific factors such as Sox10 or Pax3. The regulation of pigment cell-specific expression is also controlled by genetic elements located outside of the promoter, such as the tyrosinase distal regulatory element located at -15 kb which acts as a melanocyte-specific enhancer but also protects from spreading of condensed chromatin. Thus, by using the tyrosinase gene family as a model, it is possible to define the transcription factor networks that govern pigment production in either melanocytes or RPE.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The annual fish Nothobranchius furzeri is characterized by a natural dichromatism with yellow-tailed and red-tailed male individuals. These differences are due to different distributions of xanthophores and erythrophores in the two morphs. Previous crossing studies have showed that dichromatism in N. furzeri is inherited as a simple Mendelian trait with the yellow morph dominant over the red morph. The causative genetic variation was mapped by linkage analysis in a chromosome region containing the Mc1r locus. However, subsequent mapping showed that Mc1r is most likely not responsible for the color difference in N. furzeri. To gain further insight into the molecular basis of this phenotype, we performed RNA-seq on F2 progeny of a cross between N. furzeri male and N. kadleci female.
    BMC Genomics 09/2014; 15(1):754. DOI:10.1186/1471-2164-15-754 · 4.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Retinoic acid (RA) signaling exerts several important functions during vertebrate development. Several cell types derived from neural crest cells (NCC) have been shown to require balanced RA levels for their development. The neural crest is a transient, multipotent embryonic tissue, which also gives rise to melanophores and other pigment cell types. Here, I examined whether RA signaling is involved in NCC-derived melanophore development. My results indicate that enhanced RA levels cause hyperpigmentation in zebrafish larvae by increasing the melanoblast population, most likely by interfering with NCC development. I suggest that RA acts on NCCs, through either enhancing NCC induction, promoting proliferation, or inhibiting NCC apoptosis. It remains to be shown whether RA exerts additional functions within the melanophore lineage or, if the observations are primarily caused by RA´s well known function within NCC development.
    02/2015, Supervisor: Nicola Blum, Gerrit Begemann
  • [Show abstract] [Hide abstract]
    ABSTRACT: Large numbers of autogenous melanocytes are required when conducting studies on tissue engineering of skin and performing surgical treatment of depigmentation diseases. This study was conducted to explore the possibility of inducing differentiation of bone marrow mesenchymal stem cells (MSCs) into melanocytes (Mcs) as a means of providing autogenous melanocytes for purposes of tissue engineering and clinical treatment. MSCs were harvested from the bone marrows of black mice; and after six passages, hydrocortisone, insulin, transferrin and fibroblast growth factor were applied to induce their differentiation into Mcs. The morphological and ultrastructural characteristics of the newly differentiated cells were observed. The transcription and expression of multiple markers were examined using qRT-PCR, western-blot and immunofluorescence analysis. Cell cycle phases and yields of Mcs were analyzed by flow cytometry. Following 120 ∼180 days induction, differentiated cells were morphologically similar to Mcs, and mature melanosomes were observed. Multiple markers of melanocytes, but not melanoma cells, were expressed by the differentiated cells. Most induced melanocytes were in phase G1 or S, and yield of target cells was ∼ 80%. Melanocytes induced from bone marrow MSCs for periods of 120 ∼180 days represent a potential source of autogenous melanocytes. This article is protected by copyright. All rights reserved.
    Cell Biology International 02/2015; DOI:10.1002/cbin.10455 · 1.64 Impact Factor


Available from