Abstract |
Summary WNT1 and WNT3a have been described as having redundant roles in promoting the development of neural crest-derived melanocytes (NC-Ms). We used cell lineage restricted retroviral infections to examine the effects of WNT signaling on defined cell types in neural crest cultures. RCAS retroviral infections were targeted to melanoblasts (NC-M precursor cells) derived from transgenic mice that express the virus receptor, TVA, under the control of a melanoblast promoter (DCT). As expected, over 90% of DCT-TVA+ cells expressed early melanoblast markers MITF and KIT. However, by following the fate of infected cells in standard culture conditions, we find that only 5% of descendents were NC-Ms. The majority of the descendents were not NC-Ms, but expressed smooth muscle cell markers, demonstrating that mammalian melanoblasts are not committed to the NC-M lineage. RCAS infection of DCT-TVA+ cells demonstrated that overexpression of canonical WNT signaling genes (betaCAT, WNT3a or WNT1) can increase NC-M numbers in an endothelin dependent manner. However, WNT1 and WNT3a have different modes of action with respect to melanoblast fate. Intrinsic over-expression of betaCAT or WNT3a can increase NC-M numbers by biasing the fate of DCT-TVA+ cells to NC-Ms. In contrast, the DCT-TVA+ melanoblasts cannot respond to WNT1 signaling and do not alter their fate towards NC-M. Instead, WNT1 only increases NC-M numbers through paracrine signaling on melanoblast precursors to increase the numbers of neural crest cells that become NC-Ms.
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Authors | Karen Joyce Dunn, Matthew Brady, Christina Ochsenbauer-Jambor, Sara Snyder, Arturo Incao, William J Pavan |
Journal | Pigment cell research
(Pigment Cell Res)
Vol. 18
Issue 3
Pg. 167-80
(Jun 2005)
ISSN: 0893-5785 [Print] Denmark |
PMID | 15892713
(Publication Type: Journal Article)
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Chemical References |
- Antigens, Differentiation
- Intercellular Signaling Peptides and Proteins
- Proteins
- Proto-Oncogene Proteins
- WNT3A protein, human
- Wnt Proteins
- Wnt-5a Protein
- Wnt1 Protein
- Wnt1 protein, mouse
- Wnt3 Protein
- Wnt3A Protein
- Wnt3a protein, mouse
- Wnt5a protein, mouse
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Topics |
- Animals
- Antigens, Differentiation
(biosynthesis)
- Cell Differentiation
(physiology)
- Cell Lineage
(physiology)
- Gene Expression Regulation, Developmental
- Intercellular Signaling Peptides and Proteins
(genetics, physiology)
- Melanocytes
(cytology, physiology)
- Mice
- Mice, Mutant Strains
- Mice, Transgenic
- Muscle, Smooth
(cytology, physiology)
- Neural Crest
(cytology, embryology)
- Promoter Regions, Genetic
(genetics)
- Proteins
(genetics, physiology)
- Proto-Oncogene Proteins
(physiology)
- Signal Transduction
(physiology)
- Wnt Proteins
- Wnt-5a Protein
- Wnt1 Protein
- Wnt3 Protein
- Wnt3A Protein
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