Gleason Briana C, Crum Christopher P, Murphy George F
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Cutan Pathol. 2008 Jul;35(7):615-22. doi: 10.1111/j.1600-0560.2007.00881.x. Epub 2008 Feb 29.
The mechanisms whereby melanocytes populate the epidermis and developing hair follicles during embryogenesis are incompletely understood. Recent evidence implicates an intermediate mesenchymal stage in this evolutionary process in which HMB-45-positive melanocyte precursors ('melanoblasts') exist both in intradermal as well as intraepithelial and intrafollicular compartments. The melanocyte master transcriptional regulator, microphthalmia transcription factor (MITF), identifies mature melanocytes as well as melanocyte precursor stem cells that reside in the bulge region of the hair follicle.
To better define the use of MITF expression in the evaluation of melanocyte ontogeny, human embryonic and fetal skin samples (n = 28) at 6-24 weeks gestation were studied immunohistochemically for expression of MITF and Mart-1. Adjacent step sections were evaluated to correlate staining patterns with cell localization in the intraepidermal, intrafollicular and intradermal compartments.
At 6-8 weeks, MITF and Mart-1-positive cells were primarily intradermal with only rare positive cells in the epidermis. By 12-13 weeks, most of these cells had migrated into the epidermis, predominantly the suprabasal layers. Between 15-17 weeks, these cells localized to the basal layer and colonized developing hair follicles. Rare intradermal MITF and Mart-1 positive cells were found as late as week 20. At 18-24 weeks, MITF and Mart-1 positive cells were identified in the outer root sheath, bulge, and follicular bulge epithelium, in addition to the epidermis. Unexpectedly, weak but diffuse nuclear MITF expression was also present in the keratinocytes of the bulge area.
The in situ migratory fate of MITF/Mart-1-expressing cells in fetal skin involves a well-defined progression from intradermal to intraepidermal to intrafollicular localization. Occasional intradermal melanocytes may persist after the intraepithelial stages are completed, a finding of potential significance to melanocytic proliferations that may arise de novo within the dermis. Because MITF may play a role in stem cell maintenance, the presence of MITF in bulge epithelial cells suggests that it may be a novel marker for follicular stem cells of both epithelial and melanocytic lineage.
黑素细胞在胚胎发育过程中如何迁移至表皮和发育中的毛囊，其机制尚未完全明确。最近的证据表明，在这个进化过程中存在一个中间间充质阶段，其中HMB - 45阳性黑素细胞前体（“成黑素细胞”）存在于真皮内以及上皮内和毛囊内区域。黑素细胞的主要转录调节因子小眼畸形转录因子（MITF）可识别成熟黑素细胞以及位于毛囊隆突区的黑素细胞前体干细胞。
为了更好地界定MITF表达在评估黑素细胞个体发生中的应用，对妊娠6 - 24周的人类胚胎和胎儿皮肤样本（n = 28）进行免疫组织化学研究，检测MITF和Mart - 1的表达。对相邻的连续切片进行评估，以将染色模式与表皮内、毛囊内和真皮内区域的细胞定位相关联。
在6 - 8周时，MITF和Mart - 1阳性细胞主要位于真皮内，表皮中仅有罕见的阳性细胞。到12 - 13周时，这些细胞大多迁移至表皮，主要是基底层以上的层次。在15 - 17周之间，这些细胞定位于基底层并定植于发育中的毛囊。直到20周时仍可发现罕见的真皮内MITF和Mart - 1阳性细胞。在18 - 24周时，除了表皮外，在外根鞘、隆突和毛囊隆突上皮中也发现了MITF和Mart - 1阳性细胞。出乎意料的是，隆突区的角质形成细胞中也存在微弱但弥漫性的核MITF表达。
胎儿皮肤中表达MITF/Mart - 1的细胞的原位迁移命运涉及从真皮到表皮再到毛囊内定位的明确进展。在上皮内阶段完成后，偶尔的真皮内黑素细胞可能会持续存在，这一发现对于可能在真皮内新生的黑素细胞增殖具有潜在意义。由于MITF可能在干细胞维持中发挥作用，MITF在隆突上皮细胞中的存在表明它可能是上皮和黑素细胞谱系毛囊干细胞的一种新标记物。
