2 - 20 - PIGMENTATION AND MELANOCYTE BIOLOGY Flashcards
brown/black melanin
eumelanin
orange/yellow melanin
pheomelanin
site of melanin synthesis and storage
melanosome
variants in this receptor lead to the “red hair phenotype”—red hair, fair skin, inability to tan, and increased melanoma risk
melanocortin 1 receptor (MC1R)
Melanocyte numbers are similar in individuals of different racial backgrounds, and instead differences of pigmentation are a result of what?
amount and quality of melanin in the skin, in large part driven by variability in the **number, size, distribution, **and function of melanosomes within keratinocytes
Melanocytes are melanin-synthesizing cells of dendritic morphology located where?
within the basal layer of the epidermis, the hair bulb, and the outer root sheath of hair follicles
melanocyte:keratinocyte ratio
1:10
Within the epidermis, melanocytes are present at about 1/10th the number of keratinocytes
Special stains used to better visualize melanin
Silver stains such as the Fontana-Mason and Warthin-Starry stains
- rely on the ability of melanin to become impregnated with silver, causing intensely black precipitate in the tissue on reduction
Immunohistologic identification of melanocytes
- tyrosinase,
- MITF
- **Melan-A/Mart1
- S100
- allows identification of melanocytes in paraffin-embedded tissues as well as melanoma
Immunostaining with antibody to what is negative in normal adult melanocytes but offers additional specificity for examination of melanocytic neoplasms
**HMB-45 **(directed against gp100/PMEL17)
Identify the melanosome stage
round, approximately 0.3 µm in diameter, and contain** small intraluminal vesicles** reminiscent of multivesicular bodies of the early endosomal compartment
Stage I
Identify the melanosome stage
oval in shape and are approximately 0.5 µm in diameter and exhibit deposition of a parallel fibrillar matrix
Stage II melanosomes
Identify the melanosome stage
demonstrate deposition of pigment along the filaments
Stage III melanosomes
Identify the melanosome stage
fully melanized, with the electron-dense melanin completely obscuring the underlying structures
stage IV melanosomes
The key determinant of skin pigmentation
not melanocyte density but instead the increased ability of melanocytes from darker-skinned persons to synthesize and transfer brown-black eumelanin
Cutaneous interfollicular melanocytes are present at highest density in what areas?
facial and genital skin
lower density in the skin of the trunk and extremities
Each melanocyte contacts and delivers melanin to approximately how many keratinocytes?
40 keratinocytes
irrespective of anatomical location, via direct contacts with the melanocyte’s protruding dendrites
acral melanomas are diagnosed with high sensitivity and specificity as a result of their preferential pigmentation of what area on the acral surfaces?
eccrinerich ridges of the dermatoglyphs
- the lower permanent portion of the eccrine gland has been demonstrated as a niche for McSCs of the acral epidermis
transcription factor critical for development of the neural tube
Paired Box 3 (PAX3)
found to be mutated in human Waardenburg syndrome types 1 and 3 (hearing loss, pigmentation defect, arm and hand developmental defects).
PAX3
transcription factor first identified as being mutated in Waardenburg type IV (Waardenburg plus megacolon) and is required for development of neural, glial, and melanocyte neural crest lineages
SOX10
plays key roles in stem cell maintenance and is one of 4 transcriptions factors required for reprogramming of somatic cells to induced pluripotent stem cells
SOX2
G-protein–coupled receptor that** activates several signaling pathways**, including include protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and cAMP/PKA
Endothelin receptor type B (Ednrb)
r controls Schwann cell proliferation, migration, and myelination
ErbB2/ErbB3 heterodimer tyrosine kinase receptor
The ligand for this receptor, neuregulin, promotes the Schwann cell fate and represses the melanocyte fate.
common precursor of eumelanin and pheomelanin
dopaquinone (DQ)
melanosomes mature, the key ultrastructural feature is the appearance of what?
parallel fibrillar network; PMEL (also known as gp100 or silver) is a pigment cell–specific protein that has been shown to be the main component of these structures
this signaling has been shown to play a critical role in determining if a melanocyte produces predominantly eumelanin or pheomelanin
Melanocortin 1 receptor (MC1R) signaling
Immediate tanning occurs within minutes to hours after sun exposure, and is mainly a response to what radiation?
UVA
Delayed tanning is mainly a response to what UVR?
UVB and shorter-wavelength UVA radiation
peaks at about 3 days to 1 week after sun exposure
T/F
UV protection that is provided by melanocytes is mostly attributable to eumelanin species, whereas pheomelanin and its synthetic pathway not only lack strong UV protection but even contribute to elevated oxidative stress and measurably increased carcinogenicity.
TRUE
