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Pigment Cell Melanoma Res. 2018 Jan;31(1):95-109. doi: 10.1111/pcmr.12645. Epub 2017 Oct 13.

The patterns of birthmarks suggest a novel population of melanocyte precursors arising around the time of gastrulation.

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Genetics and Genomic Medicine, UCL Institute of Child Health, London, UK.
Paediatric Dermatology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.
Institut Curie, INSERM U1021, Normal and Pathological Development of Melanocytes, PSL Research University, Orsay, France.
Univ Paris-Sud, Univ Paris-Saclay, CNRS UMR 3347, Orsay, France.
Equipe Labellisée Ligue Contre le Cancer, Orsay, France.


Systematic work in the mouse and chicken has mapped out two neural crest-derived pathways of melanocyte precursor migration. With these in mind, this study reappraises the patterns of congenital pigmentary disorders in humans and identifies three recurrent patterns consistent across genetically different diseases. Only two of these are seen in diseases known to be melanocyte cell-autonomous. The segmental pattern correlates well with the classical dorsolateral population from animal studies, demonstrating respect of the midline, cranio-caudal axial mixing, unilateral migration and involvement of key epidermally derived structures. Importantly however, the melanocyte precursors responsible for the non-segmental pattern, which demonstrates circular, bilateral migration centred on the midline, and not involving key epidermally derived structures, have not been identified previously. We propose that this population originates around the time of gastrulation, most likely within the mesoderm, and ultimately resides within the dermis. Whether it contributes to mature melanocytes in non-disease states is not known; however, parallels with the patterns of acquired vitiligo would suggest that it does. The third pattern, hypo- or hyperpigmented fine and whorled Blaschko's lines, is proposed to be non-cell-autonomous.


birthmark; development; melanoblast; melanocytic; migration; mosaicism; non-segmental; pattern; population; segmental; spray can; vitiligo

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