International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 59 - A GENOMIC APPROACH TO ANALYZE GENES INVOLVED IN NERUAL CREST-MELANOCYTE DEVELOPMENT

Dr Laura Baxter
NIH/NHGRI
Bldg 49, Rm 4A67
49 Convent Drive
Bethesda 20892 USA

Co-Authors:  1)Loftus SK, 1)Larson DM, 1)Antonellis A, 1)Watkins-Chow D, 2)Jiang Y, 2)Chen Y, 2)Bittner M, 2)Trent J, 1)Pavan WJ
Institutions: 1)NIH/NHGRI/Genome Disease Research Branch, 2)NIH/NHGRI/Cancer Genetics Branch,

Melanocytes (MC)--pigment producing cells derived from the neural crest--are responsible for hair and skin coloration. Alterations in MC development and function result in human disorders including Waardenburg syndrome (SOX10, PAX3 and MITF), albinism (TYR, TYRP1 and DCT), and melanoma. While mutations in SOX10, PAX3 and MITF transcription factors result in MC deficiencies, few downstream targets of these genes have been identified. To identify potential targets, a 4356 human MC cDNA clone set was used for microarray expression profile analysis. Hierarchical clustering identified two gene clusters with expression patterns similar to genes with known MC function. The first 81 gene cluster (Neural Crest) contained genes previously shown to be involved in neural crest-melanocyte (NC-MC) formation, including SOX10, MITF and EDNRB. The second 72 gene cluster (Pigmentation) contained genes critical to melanin synthesis (TYRP1, CHS and DCT). Bioinformatic analysis of the cluster genes determined genomic localization, putative function, and potential association with human NC-MC disorders. Murine homologs were identified, and are being analyzed as candidates for uncloned pigmentation mutants. Developmental in situ hybridization analysis in normal and transcription factor mutant mice revealed expression patterns of these genes, thus identifying transcriptional regulatory networks for MC's and discovering novel genes involved in NC-MC development.


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