Analysis of Melanocyte Precursors in Nf1 Mutants Reveals That MGF/KIT Signaling Promotes Directed Cell Migration Independent of Its Function in Cell Survival

Wehrle-Haller, Bernhard; Meller, Margaret; Weston, James A.

doi:10.1006/dbio.2001.0167

Cited by 73 publications

(66 citation statements)

References 76 publications

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“…It is important to point out that for the purposes of the current study, TrkC and C-Kit were used only as markers for distinct neural crest subpopulations. Although these genes play important roles at least during later development of neural crest-derived cells (see Wehrle-Haller and Weston, 1997;Wehrle-Haller and Weston, 1999;Wehrle-Haller et al, 2001;Conover and Yoncopoulos, 1997;Ernfors, 2001), any gene products identifiable in living cells by our methods could potentially have been used. Indeed, because other faterestricted and partially-restricted precursors also appear to be present in nascent neural crest populations (Henion and Weston, 1997), it may be possible to identify these subpopulations using similar methods based on differentially expressed gene products.…”

Section: Discussionmentioning

confidence: 99%

Molecular identification of distinct neurogenic and melanogenic neural crest sublineages

et al. 2003

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Clonal and lineage analyses have demonstrated that although some neural crest cells have the ability to generate multiple cell types and display self-renewal ability, other crest cells generate a single or limited repertoire of cell types. However, it is not yet clear when, and in what order, crest cells become specified to adopt a particular fate. We report that the receptor tyrosine kinases TrkC and C-Kit are expressed by distinct neural crest subpopulations in vitro. We then analyzed the lineages of individual receptor-expressing crest cells and found that TrkC-expressing cells that have just emerged from the neural tube give rise to clones containing neurons or glial cells, or both, but never produce melanocytes. A short time later, TrkC-expressing cells only generate pure neuronal clones. By contrast, from their earliest appearance in neural tube outgrowths, C-Kit-expressing cells invariably give rise to clones containing only melanocytes. Our results directly demonstrate that distinct neurogenic and melanogenic sublineages diverge before or soon after crest cells emerge from the neural tube, that fate-restricted precursors are present in nascent neural crest populations and that these sublineages can be distinguished by their cell type-specific expression of receptor tyrosine kinases

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Section: Discussionmentioning

confidence: 99%

Molecular identification of distinct neurogenic and melanogenic neural crest sublineages

et al. 2003

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“…Similar phenotypes are observed in Steel (Kitl) mutant mice, which carry lesions at the Kitlg locus encoding the ligand of Kit. In mice, zebrafish and humans, Kitlg expression is required both for the migration and the survival of melanocyte precursors as well as later in the epidermis, where melanocyte precursors disperse throughout the entire embryo (Huang et al, 1992;Wehrle-Haller et al, 2001;Rawls and Johnson, 2003;Gu et al, 2009;Gu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

On the embryonic origin of adult melanophores: the role of ErbB and Kit signalling in establishing melanophore stem cells in zebrafish

et al. 2013

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SUMMARYPigment cells in vertebrates are derived from the neural crest (NC), a pluripotent and migratory embryonic cell population. In fishes, larval melanophores develop during embryogenesis directly from NC cells migrating along dorsolateral and ventromedial paths. The embryonic origin of the melanophores that emerge during juvenile development in the skin to contribute to the striking colour patterns of adult fishes remains elusive. We have identified a small set of melanophore progenitor cells (MPs) in the zebrafish (Danio rerio, Cyprinidae) that is established within the first 2 days of embryonic development in close association with the segmentally reiterated dorsal root ganglia (DRGs). Lineage analysis and 4D in vivo imaging indicate that progeny of these embryonic MPs spread segmentally, giving rise to the melanophores that create the adult melanophore stripes. Upon depletion of larval melanophores by morpholino knockdown of Mitfa, the embryonic MPs are prematurely activated; their progeny migrate along the spinal nerves restoring the larval pattern and giving rise to postembryonic MPs associated with the spinal nerves. Mutational or chemical inhibition of ErbB receptors blocks all early NC migration along the ventromedial path, causing a loss of DRGs and embryonic MPs. We show that the sparse like (slk) mutant lacks larval and metamorphic melanophores and identify kit ligand a (kitlga) as the underlying gene. Our data suggest that kitlga is required for the establishment or survival of embryonic MPs. We propose a model in which DRGs provide a niche for the stem cells of adult melanophores. KEY WORDS: Kit ligand a, ErbB, Dorsal root ganglia, Melanophore stem cells

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“…15,16) The major role of SCF in melanogenic phenomena has been thought to be targeting KIT-bearing melanoblasts or melanocytes, as evidenced by the migration of immature melanocytes from the neural crest toward the hair follicles via the epidermis. 17) In vitro, FN combined with SCF alters the attachment and migration of cultured mouse neural crest cells, which are a type of melanocytes precursors.18) Thus, it is possible that SCF, combined with matrix proteins, might play an important role in the migration of MPs from the ORS into the epidermis during the repigmentation of vitiligo.We have successfully cultured MPs of human hair follicles in vitro.4) Here, we will investigate the effects of SCF combined with matrix proteins FN, LN and CIV on the attachment and chemotaxis of MPs. In addition, the changes in the MPs cytoskeleton will also be analyzed to clarify the mechanism of how these proteins affect MPs.…”

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confidence: 99%

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confidence: 99%

Stem Cell Factor Combined with Matrix Proteins Regulates the Attachment and Migration of Melanocyte Precursors of Human Hair Follicles <i>in Vitro</i>

Wang

et al. 2013

Biological & Pharmaceutical Bulletin

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In conjunction with matrix proteins, stem cell factor (SCF) plays an important role in the migration of melanocyte precursors (MPs) derived from the mouse embryo. However, no studies have demonstrated an effect of SCF on human follicular MPs migration in vitro. In this report, first we demonstrate the immature state of the follicular MPs. Then cell attachment rate was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Standard 48-well chemotaxis chambers were used for a transfilter migration assay. F-actin was labeled by rhodamine-conjugated phalloidin, and then organization of the actin cytoskeleton was observed by confocal microscope. In the results, we directly show that MPs adhere more strongly to fibronectin (FN), laminin (LN) and type IV collagen (CIV) than to the negative control. SCF decreased the adhesion of MPs to FN and CIV. A chemotaxis analysis showed that FN and CIV have chemotactic effects on MPs. FN showed an obvious increase in chemotactic effects on MPs with SCF treatment comparing with the control group, but there were no significant changes in the levels of chemotaxis with CIV and LN when the cells were treated with SCF. SCF was chemotactic to MPs, and the presence of FN caused a statistically significant increase in MPs migration at various concentrations of SCF. Furthermore, we showed that SCF, in combination with FN, could induce an apparent increase in actin stress fiber formation in MPs. Our results indicate that SCF, in combination with matrix proteins and in particular with FN, regulates the movement of MPs by both altering cell attachment and increasing cell chemotaxis.Key words melanocyte precursor; stem cell factor; matrix protein; attachment; chemotaxis When vitiligo patients undergo repigmentation, they develop small pigmented islands that expand and coalesce to form normally pigmented skin.1) It has been demonstrated that these islands of pigmentation are derived from melanocyte precursors (MPs) in the outer root sheath (ORS) of hair follicles. 2)Although this phenomenon has been clinically well supported and MPs have been cultured successfully in vitro, little previous work has been performed to evaluate the migration capability of MPs. [3][4][5][6] When cells migrate, they synchronously attach and detach to various matrix proteins. During the repigmentation of vitiliginous skin, it is thought that MPs become activated, migrate along the basement membrane under the ORS into depigmented skin and then differentiate into mature melanocytes.2,7) The major structural proteins of the basement membrane zone (BMZ) of both normal skin and hair follicles are type IV collagen (CIV), laminin (LN) and entactin. Fibronectin (FN) present in the BMZ located under the cells of the ORS is not a normal epidermal BMZ component. It can only be identified in the epidermal BMZ during embryonic development.8,9) Therefore, there are some differences between epidermal melanocytes and MPs in the matrix proteins surrounding the BMZ. Previous authors have evaluated the impact o...

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Analysis of Melanocyte Precursors in Nf1 Mutants Reveals That MGF/KIT Signaling Promotes Directed Cell Migration Independent of Its Function in Cell Survival

Cited by 73 publications

References 76 publications

Molecular identification of distinct neurogenic and melanogenic neural crest sublineages

Molecular identification of distinct neurogenic and melanogenic neural crest sublineages

On the embryonic origin of adult melanophores: the role of ErbB and Kit signalling in establishing melanophore stem cells in zebrafish

Stem Cell Factor Combined with Matrix Proteins Regulates the Attachment and Migration of Melanocyte Precursors of Human Hair Follicles <i>in Vitro</i>

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