Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics.
MITF (microphthalmia-associated transcription factor) encodes a transcription factor with a basic-helix-loop-helix-zipper (bHLH-Zip) motif. MITF mutations occur in patients with Waardenburg syndrome type 2, a disorder associated with melanocyte abnormalities. Here we show that ectopic expression of MITF converts NIH/3T3 fibroblasts into cells with characteristics of melanocytes. MITF transfectants formed foci of morphologically altered cells, which resemble those induced by oncogenes, but did not exhibit malignant phenotypes. Instead, they contained dendritic cells that express melanogenic marker proteins such as tyrosinase and tyrosinase-related protein 1. Most cloned cells of MITF transfectants exhibited dendritic morphology and expressed melanogenic markers, but such properties were not observed in cells transfected with closely related TFE3 cDNA. Our findings indicate that MITF is critically involved in melanocyte differentiation.
Tachibana
M
M
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Rockville, Maryland 20850, USA. mtachiba@pop.nidcd.nih.gov
Takeda
K
K
Nobukuni
Y
Y
Urabe
K
K
Long
J E
JE
Meyers
K A
KA
Aaronson
S A
SA
Miki
T
T
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008544:Melanocytes / Q000166:cytology*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics; D012313:RNA; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014849:Waardenburg Syndrome / Q000235:genetics*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015415:Biomarkers; D017931:DNA Primers; D004268:DNA-Binding Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; C069203:TFE3 protein, human; D014157:Transcription Factors; D012313:RNA; D014442:Monophenol Monooxygenase