1: Exp Cell Res. 2005 Aug 1;308(1):222-35. Co-expression of SOX9 and SOX10 during melanocytic differentiation in vitro. Cook AL, Smith AG, Smit DJ, Leonard JH, Sturm RA. Melanogenix Group, Division of Molecular Genetics and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane Qld. 4072, Australia. 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. PMID: 15896776 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 2: Development. 2004 Nov;131(21):5327-39. Epub 2004 Sep 29. Canonical Wnt activity regulates trunk neural crest delamination linking BMP/noggin signaling with G1/S transition. Burstyn-Cohen T, Stanleigh J, Sela-Donenfeld D, Kalcheim C. Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical School, PO Box 12272, Jerusalem 91120, Israel. Delamination of premigratory neural crest cells depends on a balance between BMP/noggin and on successful G1/S transition. Here, we report that BMP regulates G1/S transition and consequent crest delamination through canonical Wnt signaling. Noggin overexpression inhibits G1/S transition and blocking G1/S abrogates BMP-induced delamination; moreover, transcription of Wnt1 is stimulated by BMP and by the developing somites, which concomitantly inhibit noggin production. Interfering with beta-catenin and LEF/TCF inhibits G1/S transition, neural crest delamination and transcription of various BMP-dependent genes, which include Cad6B, Pax3 and Msx1, but not that of Slug, Sox9 or FoxD3. Hence, we propose that developing somites inhibit noggin transcription in the dorsal tube, resulting in activation of BMP and consequent Wnt1 production. Canonical Wnt signaling in turn stimulates G1/S transition and generation of neural crest cell motility independently of its proposed role in earlier neural crest specification. PMID: 15456730 [PubMed - indexed for MEDLINE] --------------------------------------------------------------- 3: Curr Opin Genet Dev. 1996 Jun;6(3):334-42. Transcription factors in disease. Engelkamp D, van Heyningen V. MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK. dieter@hgu.mrc.ac.uk Mutations affecting several predominantly tissue-specific transcriptional regulators have recently been associated with disease phenotypes. Although the mutational spectrum is variable, many of the reported cases involve clear loss-of-function mutations-such as Waardenburg syndrome type 1, aniridia and Rubinstein-Taybi syndrome-suggesting that the genetic mechanism involved in disease is haplo-insufficiency. The high degree of dosage sensitivity often appears to affect only a subset of the tissues that express the gene. Position effects with cytogenetic rearrangements well outside the coding region have been implicated for four of the genes discussed: POU3F4, SOX9, PAX6, and GL13. Publication Types: Review Review, Tutorial PMID: 8791518 [PubMed - indexed for MEDLINE] ---------------------------------------------------------------