International Mammalian Genome Society

The 14th International Mouse Genome Conference (2000)

Table of Contents * Genes, Physical Mapping and Sequencing * Gene Identification * Bioinformatics * Common Resources * RIKEN Session * Functional Genomics * Complex Traits * Mutagenesis * Developmental Genetics and Differentiation * Verne Chapman Memorial Lecture I and II

I4. Neural Crest Directed Gene Transfer Demonstrates Wnt1 Role in Mlanocyte Expansion and Differentiation during Mouse Development

Karen J. Dunn ¹, Bart O. Williams², Yi Li² and William J. Pavan
¹Genetic Disease Research Branch, National Human Genome Institute Research Institute,
²Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4472 USA

Wnt1 signaling has been implicated as one factor involved in neural crest-derived melanocyte (NC-M) development. Mice deficient for both Wnt1 and Wnt3a have a marked deficiency in trunk neural crest derivatives including NC-Ms (1). We have used cell lineage-directed gene targeting of Wnt signaling genes to examine the effects of Wnt signaling in mouse neural crest development. Gene expression was directed to cell-lineages by infection with subgroup A avian leukosis virus vectors (RCAS) (2) in lines of transgenic mice that express the retrovirus receptor tv-a (2). Transgenic mice with tva in either nestin expressing neural precuror cells (line Ntva) or dopachrome tautomerase (DCT) expressing melanoblasts (line DCTtva) were analyzed. We over-stimulated Wnt signaling in two ways: directed gene transfer of Wnt1 to Ntva+ cells and transfer of b-catenin to DCTtva+ NC-M precursor cells. In both methods, NC-M expansion and differentiation were effected. Significant increases were observed in the number of NC-Ms (melanin+ and tyrosinase related protein 1 (TYRP1) + cells), the differentiation of melanin- TYRP1+ cells to melanin+ TYRP1+ NC-Ms and the intensity of pigmentation per NC-M. These data are consistent with Wnt1 signaling being involved in both expansion and differentiation of migrating NC-Ms in the developing mouse embryo. The use of lineage-directed gene targeting will allow the dissection of signaling molecules involved in NC development and is adaptable to other mammalian developmental systems.