Neural crest-directed gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development

Autor: Bart O. Williams, William J. Pavan, Yi Li, Karen J. Dunn
Rok vydání: 2000
Předmět:
Zdroj: Proceedings of the National Academy of Sciences of the United States of America. 97(18)
ISSN: 0027-8424
Popis: 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. 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 in lines of transgenic mice that express the retrovirus receptor tv-a . Transgenic mice with tva in either nestin-expressing neural precursor cells (line Ntva ) or dopachrome tautomerase (DCT)-expressing melanoblasts (line DCT tva ) were analyzed. We overstimulated Wnt signaling in two ways: directed gene transfer of Wnt1 to Ntva + cells and transfer of β-catenin to DCT tva + 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.
Databáze: OpenAIRE