WNT1 and WNT3a promote expansion of melanocytes through distinct modes of action

Pigment Cell Res. 2005 Jun;18(3):167-80. doi: 10.1111/j.1600-0749.2005.00226.x.

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.

MeSH terms

  • Animals
  • Antigens, Differentiation / biosynthesis
  • Cell Differentiation / physiology
  • Cell Lineage / physiology
  • Gene Expression Regulation, Developmental
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Melanocytes / cytology
  • Melanocytes / physiology*
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Muscle, Smooth / cytology
  • Muscle, Smooth / physiology
  • Neural Crest / cytology*
  • Neural Crest / embryology
  • Promoter Regions, Genetic / genetics
  • Proteins / genetics
  • Proteins / physiology*
  • Proto-Oncogene Proteins / physiology
  • Signal Transduction / physiology
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt1 Protein
  • Wnt3 Protein
  • Wnt3A Protein

Substances

  • 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