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 |
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Rok vydání: | 2000 |
Předmět: |
Cell signaling
animal structures Genetic Vectors Mice Transgenic Nerve Tissue Proteins Wnt1 Protein Biology Transfection Nestin Embryonic and Fetal Development Mice Organ Culture Techniques Intermediate Filament Proteins Proto-Oncogene Proteins Animals WNT1 beta Catenin Multidisciplinary Membrane Glycoproteins Wnt signaling pathway Gene Transfer Techniques Gene targeting Neural crest Zebrafish Proteins Biological Sciences Molecular biology Recombinant Proteins Intramolecular Oxidoreductases Wnt Proteins Cytoskeletal Proteins Neural Crest embryonic structures Trans-Activators Melanocytes Oxidoreductases Dopachrome tautomerase WNT3A |
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 |
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