Lecture 12 - Pigmentation

Where do melanocytes originate during development?

Melanocytes arise from the neural crest (ectoderm) and migrate out.

What are the two pathways for melanocyte migration?

Melanocytes can choose to migrate into the dermis or cross into the epidermis.

Where do melanocytes end up after migrating into the epidermis?

Epidermis → hair follicle or interfollicular epidermis.

How is melanin produced in melanocytes?

Melanin is made by melanosomes from endosomes which take up melanosomal proteins.

How are melanosomes transferred to keratinocytes?

Melanosomes are phagocytosed into keratinocytes from dendrites of melanocytes.

What triggers the skin to tan in response to sunlight?

UV light induces DNA damage, p53 stabilizes double-stranded breaks (DSBs) and upregulates POMC.
POMC gets cleaved into alpha-MSH and beta-endorphin.
ALpha-MSH binds Mc1R receptor on melanocytes to upregulate production of melanin → optical shield

What is the role of alpha-MSH in melanin production?

Alpha-MSH binds to the Mc1R receptor on melanocytes to upregulate melanin production.

Which gene is associated with melanin production?

MC1R - when receptor is bound, it upregulates melanin production

How does SLC24A5 predict skin pigmentation

Na/Ca exchanger found on melanosomes - alters pH
A allele = lighter skin
G allele = darker skin - lower pH → higher tyrosinase

What is TYR

Tyrosinase is essential for melanin production - melanogenesis enzyme

How does IRF4 modify skin pigmentation

Transcription factor for Tyrosinase gene
T allele = lighter skin (reduced expression)
C allele = darker skin

What is the difference between a melanocyte and a melanosome?

A melanocyte is a melanin-producing cell, while a melanosome is an organelle within melanocytes that produces melanin.

How does pH affect melanin synthesis?

pH determines which type of melanin is made; tyrosinase is more active at low pH → more eumelanin.

What has GWAS revealed about skin colour variation?

Skin colour variation is a complex, polygenic trait influenced by many associated loci and SNPs.

What causes blue eye colour?

Blue eye colour is caused by a lack of pigment in the outer layer of the iris and light scattering.

What SNP is a determinant in blue eyes

SNP in an enhancer within HERC2 gene
Influences ability of TFs to bind the enhancer and loop over OCA2 promoter (which creates pigmentation by encoding ion transporter in melanosomes)

What is albinism caused by?

Albinism is caused by a normal number of melanocytes but insufficient melanin synthesis due to mutations (TYR, TYPR1, OCA2, SLC45A2).

What happens in Waardenburg syndrome?

In Waardenburg syndrome, areas of iris, hair, and skin are hypopigmented due to a lack of melanocytes.

What causes different skin colours?

Differences in skin colour are due to the amount of melanin within melanosomes and the ratio of eumelanin to pheomelanin.