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

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 DCTtva) were analyzed. We overstimulated Wnt signaling in two ways: directed gene transfer of Wnt1 to Ntva(+) cells and transfer of beta-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.

Pubmed ID: 10963668

Authors

  • Dunn KJ
  • Williams BO
  • Li Y
  • Pavan WJ

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

August 29, 2000

Associated Grants

None

Mesh Terms

  • Animals
  • Cytoskeletal Proteins
  • Embryonic and Fetal Development
  • Gene Transfer Techniques
  • Genetic Vectors
  • Intermediate Filament Proteins
  • Intramolecular Oxidoreductases
  • Melanocytes
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Nestin
  • Neural Crest
  • Organ Culture Techniques
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Trans-Activators
  • Transfection
  • Wnt Proteins
  • Wnt1 Protein
  • Zebrafish Proteins
  • beta Catenin