Co-expression of SOX9 and SOX10 during melanocytic differentiation in vitro.
Investigations into pigment cell biology have relied on the ability to culture both murine and human melanocytes, numerous melanoma cell lines and more recently, murine and human melanoblasts. Melanoblast culture requires medium supplemented with a range of growth factors including Stem Cell Factor, Endothelin-3 and Fibroblast Growth Factor-2, withdrawal of which causes the cells to differentiate into melanocytes. Using the human melanoblast culture system, we have now examined the expression and/or DNA binding activity of several transcription factors implicated in melanocytic development and differentiation. Of these, the POU domain factor BRN2 and the SOX family member SOX10 are both highly expressed in unpigmented melanocyte precursors but are down-regulated upon differentiation. In contrast, the expression levels of the previously described MITF and PAX3 transcription factors remain relatively constant during the melanoblast-melanocyte transition. Moreover, BRN2 ablated melanoma cells lack expression of SOX10 and MITF but retain PAX3. A novel finding implicates a second SOX protein, SOX9, as a potential melanogenic transcriptional regulator, as its expression level is increased following the down-regulation of BRN2 and SOX10 in differentiated melanoblasts. Our results suggest that a complex network of transcription factor interactions requiring proper temporal coordination is necessary for acquisition and maintenance of the melanocytic phenotype.
Cook
Anthony L
AL
Melanogenix Group, Division of Molecular Genetics and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane Qld. 4072, Australia.
Smith
Aaron G
AG
Smit
Darren J
DJ
Leonard
J Helen
JH
Sturm
Richard A
RA
D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D018398:Homeodomain Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism*; D050809:POU Domain Factors; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D044023:Receptor, Endothelin B / Q000187:drug effects / Q000235:genetics; D055758:SOX9 Transcription Factor; D055757:SOXE Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D050809:POU Domain Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D044023:Receptor, Endothelin B; C527923:SOX10 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D055757:SOXE Transcription Factors; D014157:Transcription Factors; C085076:transcription factor Brn-2; D004247:DNA