Neural crest stem cells give rise to multiple lineages including the peripheral nervous system and melanocytes. Many birth defects, diseases and cancers including melanoma are caused by defects in neural crest expressed genes. The expression of neural crest genes is controlled by a complex transcriptional regulation. One of the transcription factors needed for appropriate expression is SOX10. The target genes of SOX10 may themselves be essential for proper neural crest development. To identify potential SOX10 target genes, we have analyzed the effects of altered SOX10 expression occurring in melanoma samples on the expression of multiple genes simultaneously using cDNA expression microarrays. Successful microarray experiments require: 1) appropriate mRNA populations to compare, 2) appropriate cDNA populations on the array, 3) critical secondary screens, and 4) defined functional assays. 1) We have and are continuing to develop sets of tools to discover and analyze genes that are involved in neural crest-derived melanocyte development and disease. We used cDNA microarray cluster analysis comparing RNA from twenty cell lines from varying stages of neural crest development and melanoma. The cDNA microarray contained over 4500 human melanocyte expressed ESTs; over 2000 mouse ESTs with similarity to known genes; and control genes with important functions in NC-M development and melanoma. Analysis of the clustered expression profiles identified two blocks of cDNAs; each containing neural crest control cDNAs as well as cDNAs that have not been attributed to development or disease. We have also developed an efficient method for functional analysis of these genes by over-expression in immortalized NC-Ms in vitro and melanoblasts in vivo. This involves using a retrovirus system to direct overexpression of genes into defined lineaegs in mice and in cell culture.
| Watkins-Chow, Dawn E; Varshney, Gaurav K; Garrett, Lisa J et al. (2017) Highly Efficient Cpf1-Mediated Gene Targeting in Mice Following High Concentration Pronuclear Injection. G3 (Bethesda) 7:719-722 |
| Silver, Debra L; Hou, Ling; Somerville, Robert et al. (2008) The secreted metalloprotease ADAMTS20 is required for melanoblast survival. PLoS Genet 4:e1000003 |
| Buac, Kristina; Pavan, William J (2007) Stem cells of the melanocyte lineage. Cancer Biomark 3:203-9 |
| Matera, Ivana; Cockroft, Jody L; Moran, Jennifer L et al. (2007) A mouse model of Waardenburg syndrome type IV resulting from an ENU-induced mutation in endothelin 3. Pigment Cell Res 20:210-5 |
| Baxter, Laura L; Hsu, Benjamin J; Umayam, Lowell et al. (2007) Informatic and genomic analysis of melanocyte cDNA libraries as a resource for the study of melanocyte development and function. Pigment Cell Res 20:201-9 |
| Brooks, Brian P; Larson, Denise M; Chan, Chi-Chao et al. (2007) Analysis of ocular hypopigmentation in Rab38cht/cht mice. Invest Ophthalmol Vis Sci 48:3905-13 |
| Hakami, Ramin Mollaaghababa; Hou, Ling; Baxter, Laura L et al. (2006) Genetic evidence does not support direct regulation of EDNRB by SOX10 in migratory neural crest and the melanocyte lineage. Mech Dev 123:124-34 |
| Hou, Ling; Arnheiter, Heinz; Pavan, William J (2006) Interspecies difference in the regulation of melanocyte development by SOX10 and MITF. Proc Natl Acad Sci U S A 103:9081-5 |
| Silver, Debra L; Hou, Ling; Pavan, William J (2006) The genetic regulation of pigment cell development. Adv Exp Med Biol 589:155-69 |
| Antonellis, Anthony; Bennett, William R; Menheniott, Trevelyan R et al. (2006) Deletion of long-range sequences at Sox10 compromises developmental expression in a mouse model of Waardenburg-Shah (WS4) syndrome. Hum Mol Genet 15:259-71 |
Showing the most recent 10 out of 28 publications
