Genetics and Genomic Medicine, UCL Institute of Child Health, London, UK.
Paediatric Dermatology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.
Pigment Cell Melanoma Res. 2018 Jan;31(1):95-109. doi: 10.1111/pcmr.12645. Epub 2017 Oct 13.
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.
系统的小鼠和鸡的研究已经绘制出了两条黑素细胞前体迁移的神经嵴衍生途径。有鉴于此，本研究重新评估了人类先天性色素紊乱的模式，并确定了三种在遗传上不同的疾病中反复出现的模式。只有两种模式出现在已知是黑素细胞自主性疾病中。节段性模式与动物研究中的经典背外侧群体很好地吻合，表明对中线的尊重、颅尾轴向混合、单侧迁移和关键表皮衍生结构的参与。然而，重要的是，负责非节段性模式的黑素细胞前体以前没有被识别，这种模式表现为以中线为中心的圆形、双侧迁移，不涉及关键的表皮衍生结构。我们提出，这个群体起源于原肠胚形成时期，最有可能在中胚层内，最终存在于真皮中。它是否在非疾病状态下有助于成熟的黑素细胞尚不清楚；然而，与获得性白癜风的模式相似，这表明它是可能的。第三类模式，即色素减退或色素沉着的细而旋状的 Blaschko 线，被认为是非细胞自主性的。
