Veterinary Dermatology 2003, 14, 57 65

Review article
The biology of melanocytes

Blackwell Publishing Ltd.

SHOLA S. SULAIMON and BARBARA E. KITCHELL

Department of Veterinary Clinical Medicine, Veterinary Teaching Hospital, University of Illinois at
Urbana-Champaign, Illinois, USA
(Received 29 June 2002; accepted 30 October 2002)

Abstract In veterinary medicine, our understanding of the biology and regulation of melanocytic function is
mostly based on information realized from human and murine studies. Improved understanding of the biology
of melanocytes is needed to develop more effective treatment regimens for malignant melanoma and other
melanocytic disorders. In vertebrates, melanocytes are well known for their role in skin pigmentation, hair and
feather coloration, and for their ability to produce and distribute melanin to surrounding keratinocytes. Enzymes
involved in melanin synthesis are present exclusively in melanosomes. The type of melanin synthesized by melanocytes in mammals is regulated at a genetic, biochemical and environmental level. These regulatory factors affect
not only the phenotypic appearance, but also the photoprotective properties of melanin. This review addresses
the biology of melanocytes, melanin synthesis and the photoprotective properties of melanin.
Keywords: keratinocytes, melanin, melanocytes, melanocytes-stimulating hormone, melanosomes, tyrosinase,
ultraviolet radiation.

INTRODUCTION
Melanocytes of the vertebrate integument are dendritic
cells of neural crest cell origin. Anatomically, melanocytes exist as relatively minor populations in the skin
(basal layer of the epidermis), eye (retinal pigment epithelium, uveal tract), hair matrix, ear (stria vascularis),
mucous membranes and central nervous system (leptomeninges).1 In the skin, melanocytes are occasionally present in the dermis in addition to the basal layer
of the epidermis. In the vertebrate epidermis, melanocytes are in close contact with surrounding keratinocytes via their dendritic processes. This close association
allows melanocytes to accomplish their primary function of producing and delivering melanin to keratinocytes, thereby providing skin pigmentation and hair and
feather coloration. Synthesis of melanin in melanocytes takes place within highly specialized membranebound intracellular organelles called melanosomes.
Melanin synthesis results in the generation of hydrogen
peroxide and quinone intermediates.2,3 These intermediates, if inappropriately processed, can damage the
cellular components of epidermal melanocytes. It is
interesting to note that nature has enigmatically confined the potentially hazardous process of melanin synthesis to the melanosomes.
The deleterious effects of melanocyte pathology are
demonstrated in several melanocytic disorders such as

Correspondence: Barbara E. Kitchell, Veterinary Medical Teaching

Hospital, University of Illinois, 1008 West Hazelwood Drive,
Urbana, IL 61802-4714, USA. Tel.: +1 217 333 3900; Fax:
+1 217 244 1475; E-mail: kitchell@ cvm.uiuc.edu.
2003 European Society of Veterinary Dermatology

melanoma, oculocutaneous albinism, vitiligo, piebaldism, Waardenburg syndrome and VogtKoyanagi

Harada syndrome. Of all the mentioned disorders,
melanoma is the most studied biological aberration of
melanocytes. Malignant melanoma (MM) is a tumour
derived from activated or genetically altered epidermal melanocytes. Malignant transformation of
melanocytes is the result of complex interactions
between genetic and environmental factors. In the
USA, MM is the most rapidly increasing malignancy
in humans and has a mortality rate that is surpassed
only by that of lung cancer.4,5 The incidence of MM
has increased dramatically in UK, Germany, Canada
and Australia. Evidence has accumulated that the
major aetiological factor for melanoma is excessive
exposure to sunlight. In humans, MM may arise from
isolated melanocytes in normal skin, but most commonly, it originates from the activated melanocytes of
solar lentigo or from benign nevomelanocytic lesions.6
These later lesions are commonly reported in sunexposed skin areas in people. In companion animals,
the most common sites of melanoma occurrence are
the head (eyes, lips, mucocutaneous junction of the
oral cavity, gums), skin and digits.7 The biological
behaviour of melanoma in dogs has been shown to be
dependent on the anatomic location of the primary
tumour. Most canine oral and digital tumours are
malignant, whereas most cutaneous melanomas are
benign. Feline melanocytic neoplasms are uncommon,
and have a high potential for malignancy independent
of the site involved.8
Rapid developments in molecular and clinical
research have revolutionized the current concepts of
the aetiology, pathogenesis and treatment of
57

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S. S. Sulaimon and B. E. Kitchell

melanoma. Intrinsic protective mechanisms within

melanocytes may modulate the treatment efficacy and
clinical outcome in patients with MM. In this review
we address melanocytes, their biology and role in melanogenesis in companion animals. The intent of this
article is to review the: histogenesis of melanocytes,
composition of eumelanin and pheomelanin, role of
tyrosinase in melanogenesis, regulators of melanogenesis, and dermoprotective functions of melanin in normal melanocytes.

MELANOCYTES IN SKIN AND HAIR

PIGMENTATION
Histogenesis of melanocytes
Melanocytes are derived from neuroectoderm (except
retinal pigment cells which are derived from the optic
cup of the forebrain).9,10 In humans, melanocytic
development begins with the migration of the melanoblast from the neural crest during embryogenesis.
Commitment of neural crest cells to the melanogenic
lineage gives rise to melanoblasts, which are able to
migrate to various destination sites and subsequently
differentiate to melanogonia and ultimately to mature
melanocytes. Homing signals that direct the migration
of melanoblasts to their destinations are yet to be characterized. In the basal layer of the epidermis, the dendritic processes of differentiated melanocytes are
interspersed between neighbouring keratinocytes.
Contact between the dendrites of melanocytes and
keratinocytes is essential for the transfer of melanincontaining melanosomes. In humans and dogs, one
epidermal melanocyte makes contact with approximately 3040 and 1020 keratinocytes, respectively.11
This association enables the melanocyte to transfer
melanin into the keratinocytes where it is the main
determinant of skin colour and helps protect against
damage from ultraviolet radiation (UVR).12,13 Epidermal melanocytes and keratinocytes constitute what is
known as the epidermal melanin unit. A similar symbiotic interaction occurs between bulb melanocytes,
and active hair follicles, by analogy constitute the follicular melanin unit.14

Types of epidermal and hair melanins and their

regulatory factors
The substance traditionally called melanin is in fact a
group of redox biopolymeric pigments synthesized by
melanocytes. Melanin is an extremely dense and insoluble chromophore of high molecular mass, synthesized
from tyrosine. Mammalian melanin is composed of
two pigments, eumelanin and pheomelanin.15 Eumelanin is a highly cross-linked, dark brown to black, insoluble
nitrogenous pigment. This pigment is predominantly
responsible for skin pigmentation, but can also be
found in hair. Pheomelanin is a yellowred alkalisoluble chromophore derived from tyrosine, in which
dopaquinone combines with glutathione or cysteine to
form cysteinyl-dopa. Intracellular levels of cysteine
play a role in whether eumelanogenesis or pheomelanogenesis will be stimulated.16 Pheomelanin is responsible for the colour of feathers and some shades of hair,
particularly shades of auburn or red. Trichochrome B
and C are the major trichochromes isolated in red hair
and red chicken feathers.14 Trichochromes are pheomelanic pigments that are acid soluble. Most melanin
occurring in nature though classified as eumelanin or
pheomelanin are rather mixed melanins. Mixed melanins contain both eumelanin and pheomelan in pigments in varying proportion. Once melanin is
produced, the melanosomes are transferred into the
neighbouring keratinocytes. Degradation of melanosomes occurs by the action of lysosomal acid hydrolase
present within keratinocytes. Degraded melanosomes
are subsequently discarded in the strateum corneum.
Steps in mammalian melanogenesis are listed in Table 1.
In humans, the pigmentation of skin and hair is
dependent on the size, number and distribution of the
melanosomes as well as on the chemical nature of the
melanins they contain.17 Melanosomes in darker individuals are larger than in their fair counterparts and
are packaged as single units rather than in groups.
Larger melanosomes have a retarding effect on
melanosome degradation in keratinocytes, thus contributing to higher levels of skin pigmentation.
Some factors known to regulate the quantity and
quality of melanins produced by melanocytes include
UVR, -melanocyte stimulating hormone (-MSH)

Table 1. Steps of mammalian melanogenesis

Step I
Step II
Step III
Step IV
Step IV
Step V
Step VI
Step VII
Step VIII
Step IX
Step X
Step XI
Step XII
Step XIII

Melanoblast migrate from the neural crest

Melanoblast differentiates to melanocyte. Clonal population of skin by melanocytes
Melanosome matrix formation
Melanogenic genes such as tyrosinase, tyrosinase related proteins and melanosomal matrix components are induced
Tyrosinase and related melanogenic proteins are synthesized
Posttranslational processing and glycosylation of tyrosinase
Fusion of vesicles to form melanosomes and initiation of melanogenesis
Control of tyrosinase activity
Control of the activity of tyrosinase related protein
Post tyrosinase modification of biosynthesis
Modification of melanin
Melanosome transfer to keratinocytes
Melanosome degradation
Melanin removal with loss of cornified cell

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59

and agouti signal protein (ASP). These factors principally modulate the expression of genes encoding
melanosomal enzymes, which in turn regulate the
eumelanin/pheomelanin switch. The interactions
between -MSH and ASP in humans and mice are
known to be critical for the switch to produce eumelanin or pheomelanin.1820 -MSH promotes eumelanin
synthesis, whereas ASP promotes pheomelanin synthesis. The effects of -MSH are mediated by the MSH
receptor (MSH-R), also known as melanocortin 1
receptor (MCR-1), which is expressed at high levels in
melanocytes.19 Agouti signal protein acts as a competitive antagonist of -MSH for the MSH-R. MSH-R is
expressed by melanocytes and is considered to be a
control point for pigmentation. MSH-R is also present
on other cells such as monocytes, endothelial cells and
keratinocytes.21,22
Tyrosinase is the key player in melanogenesis
Melanogenesis the biochemical pathway responsible
for melanin synthesis occurs in melanosomes. The
melanosome, a membrane-bound intracytoplasmic
organelle of the melanocytes originates from the endoplasmic reticulum of the melanocyte. During its development, the melanosome acquires three gene-related
melanogenic metalloenzymes, tyrosinase, tyrosinaserelated protein 1 (Trp1) and tyrosinase-related protein
2 (Trp 2). In mammals, these three related and highly
similar metalloenzymes, are involved in the catalytic
control of melanogenesis.23,24 Of these three enzymes,
tyrosinase is the most critical to melanogenesis. Mammalian tyrosinase is a bifunctional, copper-dependent
glycoprotein composed of 511 amino acids with a
molecular mass of 6075 kDa.25 Copper atoms found
at the active site of tyrosinase are an essential requirement for catalytic activity.26 Agents such as carbon
monoxide, cyanide, salicylaldoxamine and ethylthiocarbonate, indirectly inhibit tyrosinase activity by
chelating copper and abrogating its ability to bind oxygen. Synthesis of tyrosinase occurs on the ribosomes of
the rough endoplasmic reticulum (RER). Nascent
tyrosinase is transported to the Golgi complex, where
asparagine-linked glycosylation of tyrosinase is completed before export into the melanosomes. At the
Golgi complex glycosylation is essential for the normal
structure and function of tyrosinase.27,28
Tyrosinase has been divided into three domains
(Fig. 1): an inner domain that resides inside the
melanosomes, a transmembrane domain and a cytoplasmic domain that extends into the cytoplasm of
melanocytes.29 Over 90% of the tyrosinase copperbinding site is localized to the inner domain. The inner
domain has been shown to contain virtually all of the
catalytic activity that results in melanin formation
exclusively in the melanosome30 The transmembrane
and cytoplasmic domains of tyrosinase consist of short
amino acid sequences with a tail of 30 amino acids
residing in the melanocyte cytoplasm. The cytoplasmic
domain is critical for its melanogenic function and for
the cellular trafficking of tyrosinase. The cytoplasmic

Figure 1. Tyrosinase compartmentalization in the melanosome.

domain facilitates transport from the RER through the

Golgi complex to the melanosome.31 Protein kinase C (PKC-) is a signal transduction enzyme required for
the activation of tyrosinase.29 PKC- colocalizes with
tyrosinase at the melanosomal membrane and activates tyrosinase by phosphorylating the serine residues
in the C-terminal of the cytoplasmic domain.
Tyrosinase catalyses the first two rate-limiting conversion steps in the biosynthetic pathway for melanin
pigment synthesis (Fig. 2). The amino acid -tyrosine
is the metabolic precursor of melanin. First, -tyrosine
is hydroxylated to form dihydroxyphenylalanine (LDOPA). 32,33 Subsequently, L-DOPA is oxidized to
-dopaquinone. -Dopaquinone is a reactive intermediate, which is either processed into eumelanin or
pheomelanin. When thiols are absent, eumelanin is
produced. Thiols such as glutathione (GSH), cysteine
and thioredoxin have a high propensity to react with
quinone intermediates, diverting melanin pigment synthesis from eumelanin (brown/black) to pheomelanin
(red/yellow). In the absence of thiol compounds, dopaquinone spontaneously undergoes cyclization to yield
dopachrome.34 The significance of these two pathways
is discussed later. Trp2, also called dopachrome tautomerase, catalyses the tautomerization of dopachrome
into a more stable intermediate called 5,6-dihydroxyindole-2-carboxylic acid (DHICA).35 Spontaneous
decarboxylation of dopachrome can also occur, leading to 5,6-dihydroxy indole (DHI). Trp1 and tyrosinase
catalyse the conversion of DHICA to indolequinone
5,6-quinone-2-carboxylic acid a carboxylated indolequinone in mice and humans, respectively.36 Melano-

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S. S. Sulaimon and B. E. Kitchell

Figure 2. Current biosynthetic pathway of

melanin synthesis.

genesis is a hazard for melanin-producing cells, which

are endangered by the generation of reactive quinone
species.37 Quinones are highly electrophilic compounds which are very reactive depending on their
state of reduction. Quinones can undergo one electron
reduction by nucleotide adenine dinucleotide phosphate hydrogenase (NADPH) cytochrome P450
reductase to form semiquinone. Quinones can also
undergo a two-electron reduction by NAD(P)H quinone oxido reductase to form hydroquinone, a less
reactive species than semiquinone. Electron paramagnetic resonance (EPR) studies have provided evidence
for the presence of semiquinone radicals in eumelanin.38,39 Rezska and Jimbow demonstrated an increase
in the concentration of semiquinone radicals on irradiation at > 300 nm wavelength of melanocytes. Repetitive cycles of oxidation and reduction can lead to
oxidative stress and cellular damage.40 The potential
for cytotoxicity of transient molecular species generated during melanogenesis is a major biological reason
for confining melanogenesis to the membrane bound
organelle, the melanosome.
Regulators of melanogenesis
Regulatory pigmentation genes. Genes that regulate
mammalian pigmentation act at subcelluar, cellular,
tissue and environmental levels (Table 2). Pigment
genes that function at the subcellular level are
expressed specifically in melanocytes and encode
melanosome-specific proteins. These genes are located
at the albino (encodes tyrosinase), brown (encodes
Trp1), pink-eyed dilution, slaty (encodes Trp2) and silver (encodes gp 100 and Pmel 17) loci.41,42 Cellular
pigmentation genes regulate the fate of melanocytes

once localized to the basal epidermis. These genes

include the lethal spotting, microphthalmia and piebald spotting loci.17 Pigment genes that function at the
tissue level encode transcription factors or growth factors important to the function of melanocytes. Genes
that fall in this category include the steel and whitespotting loci. Finally, genes that regulate melanocyte
function at the environmental level include the agouti
locus (encodes the agouti signal protein), the extension
locus (encoded MSH receptor), and the piebald spotting locus (encodes the endothelin-1 receptor).19 The
roles of the agouti, brown and albino loci have been the
most studied in mammalian melanogenesis.
Role of hormones in melanogenesis. A number of
hormones, including adrenocorticotropic hormone
(ACTH) and -MSH, are derived from the proteolytic
cleavage of propriomelanocortin (POMC).43 POMC is
produced principally in the pars intermedia of the pituitary gland.44,45 In humans, the pituitary sources of
these hormones do not play an important role in melanogenesis because they are produced in small
amounts, however, these hormones are also produced
by melanocytes and keratinocytes and the local source
is more important in melanogenesis.46,47 -MSH is
produced in melanocytes and Langerhans cells. In
addition, ACTH can also bind to MSH receptors in
melanocytes and induce eumelanogenesis. Both
ACTH and -MSH bind to MSH receptors to enhance
melanocyte proliferation, melanogenesis and melanocyte dendrite formation.
Role of ultraviolet radiation in melanogenesis. The varying degree of skin and hair pigmentation seen in different mammals is generated by individual constitutive

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61

Table 2. Genes that regulate mammalian pigmentation

Locus

Encoded protein

Phenotypic appearance in humans and mice due to mutation in the locus

Subcellular genes albino

albino

Tyrosinase

Humans: oculocutaneous albinism type 1 (OCA 1)

Mice: absence of all pigmentation (white hair and red eyes)
Humans: a rare form of mild albinism, brown oculocutaneous
albinism (OCA 3)
Mice: brown haired mice
Humans: oculocutaneous albinism (OCA 2), blond to white hair,
pale skin and visual abnormalities
Mice: loss of function results in pink eyes and grey/yellow hair in mice
Humans: defects not yet described in man
Mice: slight dilution of black pigment.
Humans: silvering of the hair

brown

Trp 1

pink-eyed dilution

melanosome transporter

slaty

Trp 2/Dct

silver
Cellular genes
lethal spotting
piebald spotting
Tissue genes
steel
White spotting

gp 100 and Pmel 17

Endothelin 3

Humans: defects not yet described

Mice: phenotype identical to piebald spotting
Humans: piebald spotting, intestinal aganglionosis
Mice: piebald spotting

Endothelin receptor

Mast-cell growth factor

Receptor tyrosine kinase
encoded by c-Kit

Environmental factors
Agouti

Agouti signal protein

Extension locus
piebald spotting

MSH receptor
Endothelin receptor

Humans: no defects described to date

Mice: white haired mice with black eyes
Humans: piebald phenotypic appearance
Mice: similar to Steel in mice
Humans: no defects described to date
Mice: loss of function results in black hair, eumelanogenesis
pathway favoured, while a gain of function results in yellow hair,
pheomelanogenesis pathway favoured
Humans:
Humans: piebald spotting, intestinal aganglionosis
Mice: piebald spotting

genetic programmes and can be facultatively increased

by UVR exposure. Facultative pigmentation is often
divided into immediate pigment darkening and
delayed pigment darkening. Immediate pigment darkening results from translocation of melanosomes from
the perinuclear area to the dendrites. This often occurs
within seconds of UVA (320400 nm) exposure and
resolves in 13 days. Delayed pigment darkening
results from an increase in the number of melanocytes
in addition to an increase in the number of melanosomes in melanocytes and keratinocytes, and occurs
within 23 days after UVB (290320 nm) exposure.
In man, a major stimulus for facultative pigmentation is UVR. A putative melanocytic mutagen, UVR is
the most potent stimulant for growth and differentiation of melanocytes.23,48,49 The activation and differentiation of melanocytes can be induced directly by UVR
or indirectly through their interaction with surrounding UV-irradiated keratinocytes. UVR can increase the
synthesis of -fibroblast growth factor (-FGF) by
keratinocytes, which in turn stimulates proliferation
and melanogenesis of epidermal melanocytes.50,51 In
addition to increased synthesis of -FGF, exposure of
keratinocytes to UVR, results in the upregulation of
other keratinocyte-derived cytokines such as endothelin. Endothelin-1 plays an important role in stimulating melanocyte proliferation and melanization
through the G protein-coupled endothelin B receptormediated signal transduction pathway.52 Alternately,
UVR can stimulate keratinocytes to produce -MSH

which can enhance the expression of the MSH receptor

on melanocytes, resulting in increased melanogenesis
by the melanocyte.53 Mitogenic signals in addition to
UVR that have been shown to regulate melanocytic
proliferation are listed in Table 3.47,5467
The role of the c-Kit gene and its ligand in melanogenesis.
Melanocytic regulators which are not directly related
to UVR include the c-Kit gene. c-Kit is a proto-oncogene
with intrinsic tyrosine kinase activity. The gene
product of c-Kit plays a pivotal role in the normal
growth and differentiation of embryonic melanoblasts.68 In mice, c-KIT has been mapped to dominant
white spotting (w) locus, whose ligand is the product of
the sl locus (steel). The steel locus encodes stem cell
factor (SCF), which is also known as mast cell growth
factor, steel factor or KIT-ligand.69,70 Mutation in the
c-KIT receptor has been identified in human piebald
patients, suggesting that normal function of c-KIT is
required for human melanocytic development.71 Several
studies have shown that the loss of expression of c-KIT
receptor is associated with progression of human melanoma
towards the metastatic phenotype.7276 Enforced c-KIT
expression in metastatic melanoma cells significantly
inhibited their growth and metastatic potential in nude
mice. Furthermore, exposure of c-KIT-positive melanoma
cells in vitro and in vivo to SCF, the ligand for c-KIT,
triggered apoptosis of these cells but not of normal
melanocytes.68 Metastatic melanoma cells overexpress
MCAM and do not express the c-KIT receptor.

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S. S. Sulaimon and B. E. Kitchell

Table 3. Mitogenic signals in addition to UVR that have been shown to regulate melanocytic proliferation
Potent mitogens
Ultraviolet radiation54
Beta-fibroblast growth factors55,56
Cyclic adenosine monophosphate57
Hepatocyte growth factor/scatter factor58,59
Mast/stem cell factor60
Endothelin61,62
12-O-tetredecanoylphorbol-13-acetate (TPA)11
Cholera toxin11
Weak mitogens (require the presence of at least two additional potent melanocyte mitogens to exert their effect)
Melanocyte-stimulating hormone17,18
Agouti signal protein17,18
Adrenocorticotropic hormone47
Melanoma growth stimulating activity63
Gastrin releasing peptide64
Inhibitors (Factors that arrest melanocyte growth in the presence of growth factors)
Transforming growth factor 65,66
Interferon-67

Melanin pledges to protect the skin

Melanin pigments serve as not only the major determinant of phenotypic appearance, but also a protectant
against radiation. These pigments prevent sun-induced
skin damage as well as skin cancer development.14,7779
Mammalian skin is endowed with defensive mechanisms such as melanin, haircoat, Langerhan cells and
cell shedding which complement each other to minimize
UVR-induced DNA damage. The photoprotective role
of melanin is attributed to its ability to directly absorb
ultraviolet photons and reactive oxygen species (ROS)
generated by the interaction of ultraviolet photons with
membrane lipids and other cellular chromophores.
Epidermal melanin exists as a stable free radical
capable of undergoing oxidation and reduction reactions. Because of its polyquinoid nature80,81 melanin
facilitates the movement of unpaired electrons between
different energy levels, which aids in absorption of
UVR.82 The photoprotective role of both exported and
intramelanosomal melanin is attributed to the physical
and biochemical properties of its polymer form.
Impinging radiation is scattered and degraded by melanin, resulting in heat production. Radiation can also
be absorbed then oxidized in the melanin polymer. The
ability of melanin to scavenge ROS generated by UVR
exerts a cytoprotective effect on the melanocyte itself.83
Within keratinocytes, melanin tends to be distributed
in supranuclear caps that protect the nuclei from injury
caused by incoming UV photons.83,84 The induction of
DNA photoproducts such as cyclobutane pyrimidine
dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP), which are potentially carcinogenic,
is abrogated by these supranuclear caps of melanin.
Investigators have demonstrated reduced UV-induced
DNA photoproducts in human epidermis as a result of
supranuclear melanin caps. Kobayashi et al.85 showed
that epidermal cells with supranuclear melanin caps
had fewer DNA photoproducts than epidermal cells
without melanin caps. The formation of CPD and
6-4PP was reported to be lower in basal and suprabasal
cells when compared with epidermal cells in the upper

layer, which may be attributed to depth and energies of

UVR exposure. Moreover, these investigators reported
that the protection factor against both types of photo
lesions correlated with melanin concentration in epidermal cells. Also, intracellular melanin has been
shown to reduce the formation of both CPD and 6-4PP
in cultured human melanocytes and melanoma cells.82,86
That melanin provides epidermal photoprotection has
been supported by the fact that poorly melanized skin
is far more vulnerable than melanized skin to injury
caused by UVR.27

CONCLUSIONS
In summary, the similarity in pigment biology between
mammals has been demonstrated to be a complex
process. The genes and regulatory process involved are
still being identified. The role of genes and regulatory
factors regulating pigment cell proliferation are highlighted in this review. A balance in these regulatory factors is essential for normal melanocyte development
and function. Any derangement that causes a deficiency or over stimulation has an abnormal effect on
melanocytic function. An example is in MM which
arises due to dysregulation of genes and regulatory factors governing melanocytic proliferation.

ACKNOWLEDGEMENTS
The authors thank Drs Jennifer Matousek and Amy
Wiedeman for their editorial assistance.

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Rsum En mdecine vtrinaire, les connaissances de la biologie et de la rgulation de la fonction mlanocytaire sont surtout bases sur les donnes obtenues chez lhomme et chez la souris. Une connaissance plus prcise
de la biologie mlanocytaire est ncessaire pour dvelopper des traitements plus efficaces pour le mlanome malin
et dautres anomalies mlanocytaires. Chez les vertbrs, les mlanocytes sont bien connus pour leur rle dans
la pigmentation cutane, la couleur des poils et des plumes, et pour leur capacit produire et distribuer la
mlanine aux kratinocytes adjacents. Les enzymes impliques dans la synthse de mlanine sont prsentes exclusivement dans les mlanosomes. Le type de mlanine synthtise par les mlanocytes chez les mammifres dpend
de facteurs gntiques, biochimiques et environnementaux. Ces facteurs de rgulation naffectent pas uniquement
lapparence phnotypique, mais aussi les proprits photoprotectrices de la mlanine. Cette revue sintresse
la biologie des mlanocytes, la synthse des mlanines et aux fonctions photoprotectrices des mlanines.
Resumen En medicina veterinaria, nuestros conocimientos sobre la biologa y la regulacin de la funcin
melanoctica estn basados en la informacin obtenida a partir de estudios en humana y murinos. Es necesario
mejorar nuestros conocimientos sobre la biologa de los melanocitos para desarrollar pautas de tratamiento ms
efectivas de los melanomas malignos y otras alteraciones melanocticas. En vertebrados, los melanocitos se conocen bien por su papel en la pigmentacin de la piel y coloracin del pelo y plumas y por si habilidad para producir
y distribuir melanina a los queratinocitos circundantes. Los enzimas involucrados en la sntesis de melanina estn
presentes exclusivamente en los melanosomas. En los mamferos, el tipo de melanina sintetizada por los melanocitos est regulada a un nivel gentico, bioqumico y ambiental. Estos factores reguladores no slo afectan a la
apariencia fenotpica sino tambin a las propiedades fotoprotectoras de la melanina. Esta revisin versa sobre
la biologa de los melanocitos, la sntesis de melanina y las propiedades fotoprotectoras de la melanina.
Zusammenfassung Unser Wissen ber die Biologie und Regulation der Melanozytenfunktion basiert berwiegend auf Information von Studien mit Menschen und Musen. Ein besseres Verstndnis von Melanozytenbiologie ist zur Entwicklung von wirksameren Behandlungsmethoden des malignen Melanoms und anderen
melanozytischen Erkrankungen notwendig. Bei Wirbeltieren sind Melanozyten fr ihre Rolle in Hautpigmentation, Haar- und Federfrbung und fr ihre Fhigkeit, Melanin zu produzieren und an umgebende Melanozyten
zu verteilen, bekannt. Die an der Melaninsynthese beteiligten Enzyme sind ausschliesslich in Melanosomen
vorhanden. Der in Melanozyten produzierte Melanintyp ist durch genetische, biochemische und Umweltfaktoren bestimmt. Diese bersicht hat die Melanozytenbiologie, Melaninsynthese und die photoprotektiven
Eigenschaften von Melanin zum Thema.

2003 European Society of Veterinary Dermatology, Veterinary Dermatology, 14, 5765