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.
Dunn
K J
KJ
Genetic Disease Research Branch, National Human Genome Research Institute, and Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA.
Williams
B O
BO
Li
Y
Y
Pavan
W J
WJ
D000818:Animals; D003598:Cytoskeletal Proteins / Q000502:physiology; D005314:Embryonic and Fetal Development; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000502:physiology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology* / Q000502:physiology*; D008562:Membrane Glycoproteins; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D064231:Nestin; D009432:Neural Crest / Q000502:physiology*; D009924:Organ Culture Techniques; D010088:Oxidoreductases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators; D014162:Transfection; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins; D051176:beta Catenin; D010088:Oxidoreductases; C547074:Tyrp1b protein, zebrafish; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase