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Updated: Jul 7, 2026
Ex vivo Culture of Mouse Embryonic Skin and Live-imaging of Melanoblast Migration
Published on: May 19, 2014
Expression patterns of MITF during human cutaneous embryogenesis: evidence for bulge epithelial expression and
Briana C Gleason1, Christopher P Crum, George F Murphy
1Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Unlabelled:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Melanocyte (pigment cell) precursors migrate from the dermis to the epidermis and hair follicles during human development. Microphthalmia transcription factor (MITF) marks these cells and may identify follicular stem cells.
Area of Science:
- Developmental Biology
- Dermatology
- Stem Cell Biology
Background:
- Melanocyte (pigment cell) development and migration during embryogenesis are not fully understood.
- Melanocyte precursors, or melanoblasts, have been observed in intradermal, intraepithelial, and intrafollicular compartments.
- Microphthalmia transcription factor (MITF) is a key regulator of melanocyte development and is found in mature melanocytes and stem cells.
Purpose of the Study:
- To investigate the migratory patterns of melanocyte precursors during human embryonic and fetal development.
- To define the role of MITF expression in tracking melanocyte ontogeny.
- To identify potential markers for follicular stem cells.
Main Methods:
- Immunohistochemical analysis of human embryonic and fetal skin samples (6-24 weeks gestation) for MITF and Mart-1 expression.
- Correlation of staining patterns with cell localization in epidermal, follicular, and dermal compartments using adjacent step sections.
Main Results:
- Initially, MITF/Mart-1-positive cells were predominantly intradermal, migrating to the epidermis by 12-13 weeks gestation.
- By 15-17 weeks, cells colonized developing hair follicles, with persistence of rare intradermal cells up to 20 weeks.
- MITF expression was observed in epidermal, follicular, and bulge region cells, with unexpected MITF presence in bulge keratinocytes.
Conclusions:
- MITF/Mart-1-expressing cells exhibit a defined migratory path from intradermal to intraepidermal to intrafollicular locations.
- Persistent intradermal melanocytes may be relevant to dermal melanocytic proliferations.
- MITF's presence in bulge epithelial cells suggests its potential as a novel marker for both epithelial and melanocytic follicular stem cells.
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