2018 Group Project 3

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Melanocytes

Introduction

Diagram of an epidermal melanocyte and its structures

Melanocytes are a type of neural crest-derived cells in the body , most commonly found in the stratum basale, the bottom layer, of the epidermis of the skin, eyes , and to a lesser known degree, the meninges (membrane around the brain), the heart and inner ear .

Their most commonly known function is the production of melanin, melanogenesis, of which there are two types, eumelanin (black) and pheomelanin (reddish yellow) , and are responsible for the pigmentation of various parts of the human body, including the skin, hair and irises, etc. Melanogenesis has different levels, basal and activated. The basal level of melanogenesis determines an individual's skin colour and is determined by genetics, i.e. a light-skinned individual have low levels of basal melanogenesis. Activated levels of melanogenesis are usually due to external factors, such as exposure to UV-B radiation, resulting in increased levels of melanogenesis , which can be commonly seen as sunburn or tan after long exposure to sunlight.

History

The history of the discovery of the melanocyte spans about 4000 years, from when a pigmentation disorder of skin was first documented in 2200 bc, to when the melanocyte was confirmed as a pigment synthesising cell in 1917. Melanocytes were first described and named ‘chromatophores’ by Giosué Sangiovanni in 1819, who identified them in squid . Later, in 1837, Friedrich Henle identified melanocytes to be in the human skin epidermis and eye. In 1910, Ross Granville Harrison, an American anatomist, proposed that melanocytes originated from the neural crest . But it wasn’t until 1917, that Bruno Bloch identified and confirmed the enzyme tyrosinase within melanocytes to be responsible for producing melanin pigment .

Tissue Organ Structure and Function

Skin

A diagram displaying the layers of the epidermis. Melanocytes are located at the bottom layer.

Ears

Melanocytes are mainly present in the cochlea, vestibular organ and endolymphatic sac:

The cochlea of the inner ear functions as a transducer, by converting sound vibrations to electrical potentials in the auditory nerve via hair cells . In the cochlea of humans, melanocytes are found in the vascularised epithelial tissue in the intermediate layer of the stria vascularis and the modiolus, between the marginal and basal cell layers (Figure 1). During development, marginal layer cuboidal epithelium develops processes which interdigitate with the intermediate melanocytes and basal cells .Based on studies performed on mice models, it is thought that melanocytes are important for the development of the endocochlear potential (EP), produced by strial cells. Intermediate melanocytes conduct K+, which plays an important role in sound conductance, as it flows from the endolymph into the ciliated epithelial cells of the ear via mechano-electrical channels. This influx of K+ is driven by a combination of the membrane potential of these ciliated epithelial cells, and the EP. A study on guinea pig models showed that blocking the K+ channels of melanocytes produces a lower EP . This study agrees with evidence showing that mice deficient in cochlea melanocytes have a lower EP, requiring a greater sound stimulus to produce an action potential .

Figure 1: Diagram of the Stria Vascularis, containing the marginal cells, intermediate melanocytes and basal cells. It shows marginal cell extensions intercalating with melanocytes, and the K+ ion channels involved in generating the EP .

Figure 2: The cochlea of a Wv/Wv viable dominant spotting mutant, showing the distribution of melanocytes as dots within the Stria Vascularis of the left cochlea .

Eyes

The uveal tract (iris, ciliary body and choroid) and conjunctiva normally contains melanocytes derived from the neuro-ectodermal neural crest. Peri-orbital soft tissue is also derived from the embryonic neural crest. On the other hand, pigmented melanocytes (such as those found on the retina) were derived from the neuroepithelium or from different layers of the optic cup. Eye melanocytes (like all other melanocytes) differentiate into melanin-producing cells, which in this case determines a person's eye colour, protect the eye from UV radiation and many ocular diseases that can cause blindness, including age-related macular degeneration. Melanocytes found in the eye are not able to participate in regeneration unlike epidermal melanocytes.

Heart

Figure 3. A differential interference contrast (DIC) microscopical image of a cardiac melanocyte present in an isolated atrial cell of an embryonic mouse pup. The white arrow indicates the cardiac melanocyte that is found amidst the atrial myocytes that are marked by the yellow arrowheads.

Central Nervous System

A diagram displaying the layers in the skull, including the meninges.

Melanocytes can also be found within the Central Nervous System, primarily in the leptomeninges , which consists of the inner two layers membranes of the meninges, the pia mater and arachnoid, which encapsulate the brain and the spinal cord. While its function within the meninges is unknown, they are essential to the health of the meninges, with their removal increases the risk of aseptic meningitis . Furthermore, due to its receptivity to the same signalling molecules as neurons, scientists can study diseases afflicting the central nervous system using it as a model .

Animal Models

Potential Animal Models= Opossum, Platyfish, Zebrafish, Genetically Engineered Mice (GEM)- developments for understanding the biological events in naves and melanoma formation

Current Research

Potential Current Research= Using pluripotent stem cells to generate melanocytes, Regulating melanocytes for neural trans-differentiation

Abnormalities

Eyes

Melanoma that occurs in the eye is known as uveal melanoma. This is an uncommon form of cancer that only accounts for about 3% of all melanomas. The risk factors of this cancer are light skin colour, red or blonde hair and blue or light irises.