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From neural crest cells to melanocytes: cellular plasticity during development and beyond

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Abstract

Here, we review melanocyte development and how the embryonic melanoblast, although specified to become a melanocyte, is prone to cellular plasticity and is not fully committed to the melanocyte lineage. Even fully differentiated and pigment-producing melanocytes do not always have a stable phenotype. The gradual lineage restriction of neural crest cells toward the melanocyte lineage is determined by both cell-intrinsic and extracellular signals in which differentiation and pathfinding ability reciprocally influence each other. These signals are leveraged by subtle differences in timing and axial positioning. The most extensively studied migration route is the dorsolateral path between the dermomyotome and the prospective epidermis, restricted to melanoblasts. In addition, the embryonic origin of the skin dermis through which neural crest derivatives migrate may also affect the segregation between melanogenic and neurogenic cells in embryos. It is widely accepted that, irrespective of the model organism studied, the immediate precursor of both melanoblast and neurogenic populations is a glial-melanogenic bipotent progenitor. Upon exposure to different conditions, melanoblasts may differentiate into other neural crest-derived lineages such as neuronal cells and vice versa. Key factors that regulate melanoblast migration and patterning will regulate melanocyte homeostasis during different stages of hair cycling in postnatal hair follicles.

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Abbreviations

Bcl2:

B-cell lymphoma 2

BMP:

Bone morphognetic protein

BQ778:

Selective EDNRB antagonist

Col17a1:

Collagen type XVII alpha 1

CREB:

cAMP-responsive element binding protein

Dct:

Dopachrome tautomerase

Dhh:

Hedgehog

ECM:

Extracellular matrix

EDN1:

Endothelin 1

EDNRB:

Endothelin receptor type B

ET3:

Endothelin 3

FGF:

Fibroblast growth factor

FOXD3:

Forkhead box D3

hESC:

Human embryonic stem cells

JAMs:

Junctional adhesion molecules

KIT/KITL:

c-kit/Kit ligand

KIT:

Kit proto-oncogene

MC1R:

Melanocortin 1 receptor

Mitf:

Microphthalmia-associated transcription factor

MPNST:

Malignant peripheral nerve sheath tumor

MSA:

Migration staging area

MSX1/2:

Msh homeobox 1/2

Nf1B:

Neurofibromin 1b

NGFRp75:

Nerve growth factor receptor

PAX3:

Paired Box 3

PLP:

Proteolipid protein

SCP:

Schwann cell precursor

SLUG:

Snail family transcription factor 2

Smad:

Mother against decapentaplegic homolog

SNAIL:

Snail family transcription factor 1

SOX10:

(Sex determining region Y)-box 10

TGFβ:

Transforming growth factor beta

Tyr:

Tyrosinase

Tyrp1/2:

Tyrosinase-related protein 1/2

WNT:

Wingless-type MMTV integration site family

ZIC1/2:

Zinc finger of the cerebellum 1/2

ZEB1/2:

Zinc finger E-box binding homeobox 1/2

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Acknowledgements

G.B.’s laboratory is supported by the Fonds Wetenschappelijk Onderzoek (3G050217W), the Geconcerteerde Onderzoeksacties Ghent University (GOA-01GB1013W), Vlaamse Liga tegen Kanker (365U8914U) and the Stichting tegen Kanker (FAF-F/2016/814).

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Authors and Affiliations

  1. Molecular and Cellular Oncology Laboratory, Department of Biomedical Molecular Biology, Ghent University, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium

    Niels Vandamme & Geert Berx

  2. DAMBI, VIB Center for Inflammation Research, Ghent, Belgium

    Niels Vandamme

  3. Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium

    Niels Vandamme

  4. Cancer Research Institute Ghent (CRIG), Ghent, Belgium

    Niels Vandamme & Geert Berx

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  1. Niels Vandamme
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Vandamme, N., Berx, G. From neural crest cells to melanocytes: cellular plasticity during development and beyond. Cell. Mol. Life Sci. 76, 1919–1934 (2019). https://doi.org/10.1007/s00018-019-03049-w

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