Mysteries of the Mighty Melanocytes

Jul 26, 2016 | Disease Models

Melanocytes are cells that produce melanin, the pigment present in our skin, eyes, and hair. iPS-derived melanocytes are used in models of skin disease, drug toxicity assays, skin bioprinting and in cell therapy R&D. Previously, we looked at the role of melanin and what happens when melanin production is dysfunctional and this left us with some interesting questions:

  • Why do we have melanocytes in many parts of the body that are not exposed to the sun including the brain, lungs and heart?
  • Why is hearing affected in melanocyte-deficient conditions like Waardenburg Syndrome?

These questions raise two deeper scientific questions:

  • Are melanocytes more than just pigment-producing cells?
  • Is melanin more than a pigment?

Answering these questions could affect how we diagnose and treat many types of diseases where melanocytes are dysfunctional, including albinism and skin cancer, but also could make us wonder if these cells play a role in the diseases of the other organs and tissues where they can be found – they could be important in a wide range of diseases from neurological disorders to genetic disorders.

Let’s dive into what the research tells us!

A Closer Look at Albinism

Albinism is characterized by impaired melanin production or distribution caused by the presence of certain genetic defects. Symptoms include: reduced or absent coloring of the skin and hair and in the irises, sometimes completely, other times to certain degrees or in patches. Interestingly, albinism is often associated with several other issues including:

(i) eyes that move out of sync with one another (strabismus)
(ii) light sensitivity (photophobia)
(iii) rapid eye movements (nystagmus)
(iv) impaired vision such as astigmatism or functional blindness

Each of these eye symptoms are the result of incorrect development of the optic nerve pathways from the eye to the brain as well as from the retinas not developing normally.

There are several different types of albinism:

Type of Albinism


The Genetics

Oculocutaneous Albinism (oca)

Alterations in hair and eye color.

Four subtypes, OCA 1-4, caused by a mutation in one of four gene. Each subtype tends to be found in distinct parts of the world.

X-linked Ocular Albinism

Vision issues and sometimes lighter hair, eyes and skin.

Occurs almost exclusively in males as it is a genetic mutation of the X chromosome. Thus only one copy is needed in males for the condition to be present.

Hermansky-pudlak Syndrome

Very similar symptoms to OCA but may also develop lung and bowel diseases, or a bleeding disorder.

Rare. Caused by the mutation of one of eight genes.

Chediak-higashi Syndrome

Similar symptoms to OCA but also presents with white blood cell abnormalities and immunodeficiencies.

Rare. Caused by mutations in the LYST gene.

OCA is the most common form of albinism with an estimated rate of occurrence of 1 in every 20,000 births. In OCA-1, the role of melanocytes in embryonic development can be seen. Here, misrouting of the optic nerves at the chiasm can be seen. How could pigment-producing cells play a role in optic nerve development?


Melanocytes make a protein called melanocortin 1 receptor (MC1R). This is important in the regulation of the quality and quantity of their melanin production. MC1R is controlled by two protein: melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH). These activate the melanogenic cascade. This cascade creates eumelanin and agouti signaling protein (ASP). ASP stimulates the production of pheomelanin, but it also modulates the expression of genes involved in morphogenesis, particularly in the development of the nervous system!

It would seem our respectable melanin-producers have some side jobs we didn’t know about!

But there’s more…

Melanocytes and Waardenburg Syndrome (WS)

Not only do melanocytes play a crucial role in our ability to see but they can also take credit for helping with normal hearing!

There are four types of WS and half a dozen genes have been implicated as contributors to this syndrome. These genes are involved in the development and formation of several types of cells, including melanocytes.

The symptoms of WS vary from case-to-case but primary features often include distinctive facial characteristics; reduced pigmentation of the hair, the skin, and/or the iris of both eyes and/or congenital deafness.

Research in WS has shown that melanocytes play a pivotal role in the normal function of the middle ear. Melanocytes should be present in the stria vascularis for normal cochlear function. Histopathologic examination of the inner ears of individuals with WS shows absent Organs of Corti, atrophy of the spinal ganglion and reduced numbers of nerve fibers.

If you’re still not convinced that these cells deserve to be known as so much more than the cells that help us get a tan, let’s look at the melanocytes in the brain!

Parkinson’s Disease

As we discussed previously, there are three types of melanin, or at least two distinct types, and a third that is a mix of them plus some other ingredients. The latter, is called neuromelanin. It is composed of a complex of the two other types of melanin eumelanin and pheomelanin, a eumelanin-covering on a pheomelanin, aliphatics and peptides core. Neuromelanin is found primarily in the dopaminergic neurons of the substantia nigra and in the locus coerulus.

Interestingly, the selective loss of dopaminergic neurons containing neuromelanin is associated with Parkinson’s disease. It is thought to have a neuroprotective role through the removal of reactive oxygen species and metal. One paper showed that the autograft cell transplantation of tyrosine-secreting cells from the skin, including melanocytes, to the brain ameliorated symptoms of the disease. This gives interesting food for thought of the potential of treating Parkinson’s by targeting our suntan cells.

Other roles proposed for melanocytes include a part in controlling our respiratory rhythm and in the stiffness of the tricuspid valve of the heart but their role in adipose tissue is still unclear.

It’s clear that melanocytes moonlight in many other jobs around the body and that there is still much to learn about them!

For further reading, I greatly enjoyed reading: “What are melanocytes really doing all day long…? : from the ViewPoint of a keratinocyte: Melanocytes – cells with a secret identity and incomparable abilities”, by Michaela Brenner and Vincent J. Hearing.

Article by Olwen Reina. Contact Olwen at