Signaling and transcriptional regulation in the neural crest-derived melanocyte lineage: interactions between KIT and MITF

Development ◽  
2000 ◽  
Vol 127 (24) ◽  
pp. 5379-5389 ◽  
Author(s):  
L. Hou ◽  
J.J. Panthier ◽  
H. Arnheiter
Keyword(s):  
Neural Crest ◽  
Cholera Toxin ◽  
Leucine Zipper ◽  
Pigment Cell ◽  
Neural Crest Cell ◽  
Tyrosine Kinase Receptor ◽  
Lacz Gene ◽  
Helix Loop Helix ◽  
Complex Interactions ◽  
Tyrosinase Expression

Genetic and cell culture analyses have shown that the development of melanocytes from neural crest-derived precursor cells critically depends on the tyrosine kinase receptor KIT and the basic-helix-loop-helix-leucine zipper transcription factor MITF. KIT and MITF show complex interactions in that MITF is needed for the maintenance of Kit expression in melanoblasts and KIT signaling modulates MITF activity and stability in melanocyte cell lines. Using primary neural crest cell cultures from embryos homozygous for a Kit null allele marked by an inserted LacZ gene (Kit(W-LacZ)), we show that the onset of Mitf expression in melanoblasts does not require KIT. In fact, provided that the melanocyte growth factor endothelin-3 is present, a small number of MITF/beta-Gal-positive cells can be maintained for at least 2 weeks in Kit(W-LacZ)/Kit(W-LacZ) cultures. These cells express several pigment cell-specific genes that are thought or have been shown to be activated by MITF, including dautochrome tautomerase, pMel 17/Silver and tyrosinase-related protein-1, but lack expression of the MITF target gene tyrosinase, which encodes the rate-limiting enzyme in melanin synthesis. Consequently, the cells remain unpigmented. Addition of cholera toxin, which elevates cAMP levels and mimics part of the KIT signaling pathway, increases the number of MITF-positive cells in Kit(W-LacZ)/Kit(W-LacZ) cultures, leads to tyrosinase expression, and induces the differentiation of melanoblasts into mature, pigmented melanocytes. Even when added on day 5–6 of culture, cholera toxin still rescues tyrosinase expression and differentiation. The results thus demonstrate that the presence of MITF is not sufficient for tyrosinase expression in melanoblasts and that KIT signaling influences gene expression during melanocyte development in a gene-selective manner.

scholarly journals Melanocyte development in vivo and in neural crest cell cultures: crucial dependence on the Mitf basic-helix-loop-helix-zipper transcription factor

Development ◽  
1997 ◽  
Vol 124 (12) ◽  
pp. 2377-2386 ◽  
Author(s):  
K. Opdecamp ◽  
A. Nakayama ◽  
M.T. Nguyen ◽  
C.A. Hodgkinson ◽  
W.J. Pavan ◽  
...  
Keyword(s):  
Neural Crest ◽  
Cell Cultures ◽  
Neural Crest Cell ◽  
Tyrosine Kinase Receptor ◽  
Wild Type ◽  
Helix Loop Helix ◽  
Migration Pathway ◽  
Endothelin 3 ◽  
Crest Cell

The more than 20 different Mitf mutations in the mouse are all associated with deficiencies in neural crest-derived melanocytes that range from minor functional disturbances with some alleles to complete absence of mature melanocytes with others. In the trunk region of wild-type embryos, Mitf-expressing cells that coexpressed the melanoblast marker Dct and the tyrosine kinase receptor Kit were found in the dorsolateral neural crest migration pathway. In contrast, in embryos homozygous for an Mitf allele encoding a non-functional Mitf protein, Mitf-expressing cells were extremely rare, no Dct expression was ever found, and the number of Kit-expressing cells was much reduced. Wild-type neural crest cell cultures rapidly gave rise to cells that expressed Mitf and coexpressed Kit and Dct. With time in culture, Kit expression was increased, and pigmented, dendritic cells developed. Addition of the Kit ligand Mgf or endothelin 3 or a combination of these factors all rapidly increased the number of Dct-positive cells. Cultures from Mitf mutant embryos initially displayed Mitf-positive cells similar in numbers and Kit-expression as did wild-type cultures. However, Kit expression did not increase with time in culture and the mutant cells never responded to Mgf or endothelin 3, did not express Dct, and never showed pigment. In fact, even Mitf expression was rapidly lost. The results suggest that Mitf first plays a role in promoting the transition of precursor cells to melanoblasts and subsequently, by influencing Kit expression, melanoblast survival.

Structural and compositional divergencies in the extracellular matrix encountered by neural crest cells in the white mutant axolotl embryo

Development ◽  
1990 ◽  
Vol 109 (3) ◽  
pp. 533-551 ◽  
Author(s):  
R. Perris ◽  
J. Lofberg ◽  
C. Fallstrom ◽  
Y. von Boxberg ◽  
L. Olsson ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Neural Crest ◽  
Pigment Cell ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Ruthenium Red ◽  
Neural Crest Cell Migration ◽  
White Mutant ◽  
Crest Cell

The skin of the white mutant axolotl larva is pigmented differently from that of the normal dark due to a local inability of the extracellular matrix (ECM) to support subepidermal migration of neural crest-derived pigment cell precursors. In the present study, we have compared the ECM of neural crest migratory pathways of normal dark and white mutant embryos ultrastructurally, immunohistochemically and biochemically to disclose differences in their structure/composition that could be responsible for the restriction of subepidermal neural crest cell migration in the white mutant axolotl. When examined by electron microscopy, in conjunction with computerized image analysis, the structural assembly of interstitial and basement membrane ECMs of the two embryos was found to be largely comparable. At stages of initial neural crest cell migration, however, fixation of the subepidermal ECM in situ with either Karnovsky-ruthenium red or with periodate-lysine-paraformaldehyde followed by ruthenium red-containing fixatives, revealed that fibrils of the dark matrix were significantly more abundant in associated electron-dense granules. This ultrastructural discrepancy of the white axolotl ECM was specific for the subepidermal region and suggested an abnormal proteoglycan distribution. Dark and white matrices of the medioventral migratory route of neural crest cells had a comparable appearance but differed from the corresponding subepidermal ECMs. Immunohistochemistry revealed only minor differences in the distribution of fibronectin, laminin, collagen types I, and IV, whereas collagen type III appeared differentially distributed in the two embryos. Chondroitin- and chondroitin-6-sulfate-rich proteoglycans were more prevalent in the white mutant embryo than in the dark, especially in the subepidermal space. Membrane microcarriers were utilized to explant site-specifically native ECM for biochemical analysis. Two-dimensional gel electrophoresis of these regional matrices revealed a number of differences in their protein content, principally in constituents of apparent molecular masses of 30–90,000. Taken together our observations suggest that local divergences in the concentration/assembly of low and high molecular mass proteins and proteoglycans of the ECM encountered by the moving neural crest cells account for their disparate migratory behavior in the white mutant axolotl.

Cyclical fate restriction: a new view of neural crest cell fate specification

Development ◽  
2021 ◽  
Vol 148 (22) ◽  
Author(s):  
Robert N. Kelsh ◽  
Karen Camargo Sosa ◽  
Saeed Farjami ◽  
Vsevolod Makeev ◽  
Jonathan H. P. Dawes ◽  
...  
Keyword(s):  
Neural Crest ◽  
Cell Fate ◽  
Pigment Cell ◽  
Neural Crest Cell ◽  
Neural Crest Cells ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
Dynamic View ◽  
Fate Restriction ◽  
Crest Cell

ABSTRACT Neural crest cells are crucial in development, not least because of their remarkable multipotency. Early findings stimulated two hypotheses for how fate specification and commitment from fully multipotent neural crest cells might occur, progressive fate restriction (PFR) and direct fate restriction, differing in whether partially restricted intermediates were involved. Initially hotly debated, they remain unreconciled, although PFR has become favoured. However, testing of a PFR hypothesis of zebrafish pigment cell development refutes this view. We propose a novel ‘cyclical fate restriction’ hypothesis, based upon a more dynamic view of transcriptional states, reconciling the experimental evidence underpinning the traditional hypotheses.

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