ACVD Exam > Structure and Function - Melanogenesis > Flashcards

Structure and Function - Melanogenesis Flashcards

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1
Q

From what cells to melanoblasts originate?

A

embryonic neural crest cells

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2
Q

Main signaling molecules that that influence melanoblast migration and differentiation

A

Wnt
Endothelin-3 (ET3)
Bone morphogenetic proteins (BMPs)
Stem cell factor
Hepatocyte growth factor

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3
Q

Two main locations of melanocytes in the skin

A
  • epidermis (primarily basal layer)
  • hair follicles (outer root sheath and hair matrix)
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4
Q

Non-skin locations of melanocytes

A
  • uvea
  • cardiovascular system
  • cochlea (stria vascularis)
  • CNS
  • adipose
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5
Q

Main adhesion molecule that mediates adhesion between melanocytes and keratinocytes

A

E-cadherin

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6
Q

Lysosome-like organelles in which melanin pigments are synthesized and stored

A

Melanosomes

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7
Q

Special stains that can be used to visualize melanocytes (3)

A
  • DOPA oxidase reaction
  • Fontana-Masson stain
  • Schmorl’s method
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8
Q

3 main functions of melanocytes

A
  • cosmetic appearance
  • protection against ionizing radiation
  • scavenger of cytotoxic free radicals and intermediates
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9
Q

2 main melanin types and the colors they produce

A
  • eumelanin (black-brown)
  • pheomelanin (red-yellow due to higher levels of sulfur)
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10
Q

Key steps for synthesis and distribution of melanin in the epidermis

A
  • transcription of proteins required for melanogenesis
  • melanosome biogenesis
  • transport of the melanosome to the tips of melanocyte dendrites
  • transfer of the melanosomes to keratinocytes
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11
Q

The common pathway from which all melanins arise involves what key intermediate?

A

dopaquinone

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12
Q

Rate limiting step in melanin synthesis

A

Conversion of Tyrosine to L-DOPA by the copper containing enzyme tyrosinase

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13
Q

Critical co-factor for the enzyme tyrosinase in the rate-limiting step of melanin synthesis

A

Copper

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14
Q

Transcription factor primarily responsible for regulation of melanogenesis

A

MITF (microphthalmia-associated transcription factor)

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15
Q

Roles of Wnt (wingless-related integration site) in melanogenesis

A
  • Wnt acts on melanoblasts to maintain MITF expression and promote melanoblast differentiation into melanocytes
  • critical role in the development of melanocytes from neural crest cells
  • role in melanoblast differentiation into melanocytes
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16
Q

Alpha-MSH, one of the main drivers of melanogenesis, activates the process of melanogensis through the binding of what receptor?

A

MC1-R

Melanocortin/alpha-MSH binds MC1-R => stimulates eumelanin production

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17
Q

UV Radiation upregulates levels of what factors involved in melanogenesis?

A
  • POMC (alpha-MSH is cleaved from this protein)
  • Alpha-MSH
  • ACTH
  • MC1R
  • MITF
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18
Q

Alpha-MSH, ACTH, Endothelin1, steel (stem cell) factor, leukotrienes (LTB4, LTC4), prostaglandins (PGE2, PGF2alpha), UV radiation, nitric oxide, histamine and neurotrophins are inhibitors or stimulators of melanogenesis?

A

Stimulators

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19
Q

TNF-alpha, IL-1, IL-6, and BMP-4 are inhibitors or stimulators of melanogenesis?

A

Inhibitors

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20
Q

A family of peptides that are important regulators of melanogenesis and involved in the late steps of melanoblast migration from the dermis to the basal layer of the epidermis

A

Endothelins (ET3 is especially significant)

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21
Q

Receptor for ET3

A

EdnrB (Endothelin receptor type B)

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22
Q

Melanosomes are tranported along the melanocyte dendrites attached to what two microtubule proteins?

A

dyneins and kinesins

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23
Q

Importance of myosin-Va

A

Role in actin binding and melanosome transfer at the dendrite tip

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24
Q

Clinical signs of Type IV Waardenburg Syndrome

A

varying degrees of deafness and facial bone defects and by variation in pigmentation of the skin, hair, or eyes

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25
Type IV Waardenberg syndrome is caused by a mutation of the gene encoding what?
EdnrB (leads to failure of migration and development of melanoblasts)
26
Domestic(ish) animal species somewhat commonly affected by Waardenburg syndrome
ferrets
27
Defects in what genes have been implicated in various types of Waardenburg syndrome?
PAX3, SOX10, MITF, SNAI2, **EDNRB**, EDN3
28
Chediak-Higashi Syndrome is an autosomal rescessive genetic disorder caused by a defect in what gene? What does that defect cause at a cellular level?
- LYST (encodes CHS-1 protein) - defective lysosome and vesicular transport -> Failure of phagolysosome formation and increased susceptibility to disease *large peroxidase positive lyosomes in eos, neuts, and basophils*
29
Clinical signs of Chediak-Higashi syndrome
- Albinism or lighter hair coat and photophobia - Can also see: recurrent infections, neurologic signs, pulmonary fibrosis, and bleeding abnormalities
30
Chediak-Higashi syndrome has been reported in a number of animals including cats Hereford cattle, Australian blue rats, mice, mink, foxes, and an albino orca. In what species and breed is this syndrome most commonly reported?
Persian cats (blue-smoke hair color and yellow eyes)
31
Where do melanocytes reside in the cochlea?
Stria vascularis
32
What melanocyte transcription factor is essential for the development of and maturation of the cochlea?
Mitf
33
Oculocutaneous albinism (hypomelanosis of the skin, hair, and eyes) has been reported to occur due to defects in what genes (3)?
- TYR (tyrosinase - ie siamese cats with dif color hair depending on temp) - TYRP1 (Tyrosinase-related protein 1) - SLC45A2
34
Is piebaldism autosomal recessive or dominant?
Dominant
35
Piebaldism has been reported to occur as a result of genetic mutations in what 3 genes?
**c-Kit** SCF (stem cell factor)/Steel factor SLUG
36
Clinical signs of piebaldism in animals
whitea coat appearing to have pigmented spots on a pigmented background of hair, feathers or scales (generally cosmetic)
37
Lethal lavender foal syndrome is fatal in affected Arabian horses (neuro and skin signs). It occurs due to a genetic mutation in what gene?
MYO5A (myosin-Va plays an important role in melanosome transfer from melanocytes to keratinocytes)
38
Mutation in the same gene that causes lethal lavender foal syndrome (MYO5A - Myosin-Va) causes what syndrome in people?
Griscelli-Pruniéras
39
What causes hair shafts to fracture in color dilution of alopecia?
macromelanosomes (significantly enlarged melanosomes)
40
Vitiligo is an acquired, mutifactorial disorder that is suspected involve what two broad types of mechanisms?
- autoimmune - genetic
41
In vitiligo, destruction of melanocytes is suspected to be mediated by what type of cells?
Auto-reactive cytotoxic T cells
42
Histologic findings in vitiligo
complete lack of melanocytes with out inflammatory infiltrate (in early lesions, some melanocytes and inflammatory infiltrate may still be present)
43
Uveodermatologic syndrome (Vogt-Koyanagi-Harada syndrome) is an autoimmune disease that targets melanin containing tissue. Auto-reactivity in this disease is mediated by what type of cells?
T-cells
44
Clinical signs of uveodermatologic syndrome in humans
leukoderma, uveitis, aseptic meningitis, dyascusis (hearing impairment), tinnitus (ringing in the ears), leukotrichia, and alopecia
45
Clinical signs of Uveodermatologic syndrome in dogs
- acute uveitis -> can result in blindness due to secondary glaucoma as well as other ocular abnormalities - depigmentation of the hair, usually on the face and the skin of the nose, lips, eyelids and occasionally the footpads, scrotum, anus, and hard palate
46
Breeds most commonly affected by uveodermatologic syndrome
Akitas, Huskies, Malamutes, Samoyed (arctic breeds)
47
Cause of graying hairs
- decline in melanogenically active melanocytes in the hair bulb (determined by age and genetics) - ineffective melanosome transfer
48
Most common cause of acquired pigmentation in dogs and cats
Post-inflammatory hyperpigmentation
49
What is feline acromelanism?
genetic form of oculocutaneous albinism and seen in Siamese, Himalayan, Balinese, Birman, Burmese, and Singapura cats
50
In cats with acromelanism, the activity of what enzyme is temperature sensitive?
tyrosinase
51
Leukoderma in horses is common and can be incited by what factors?
onchocerciasis, dourine, herpes coital exanthema, lupus erythematosus, pressure sores, ear papillomas, ventral midline dermatitis, regressing viral papillomatosis, or freezing and burn
52
Disorders of Melanoblast migration (3)
Piebaldism Waardenburg syndrome Tietz syndrome
53
Clinical signs of Tietz syndrome (cause by MITF mutation)
generalized hypopigmentation of skin, hair and eyes as well as congenital deafness, microphthalmia *human thing?*
54
Lethal white foal syndrome is the result of what genetic mutation?
EDNRB
55
Localization and maintenance of melanocyte stem cells to epithelial niches depends on what type of molecular interaction?
KIT/KIT-ligand interactions with keratinocytes, cadherins, integrines, and matrix factors
56
The gray horse phenotype is caused by an autosomal dominant mutation in what gene?
STX17
57
What is Hermansky-Pudlak syndrome?
a heterogeneous group of autosomal-recessive disorders in humans that cause cutaneous and ocular hypopigmentation along with variable extra-pigmentary clinical signs - Most commonly caused by a defect in BLOC genes
58
Types of Hermansky-Pudlak syndrome have been reported in what species/breeds?
- Type 3 in Frenchies d/t BLOC gene mutation - produces cocoa colored hair coat - Type 5 in Sphinx cats - light-brown skin, yellow irises, red eye effect - Type 5 in horses - white markings
59
Leukoderma seems most common in what horse breed?
Arabians - also called Arabian fading syndrome or pinky syndrome (congenital autoimmune disease)
60
Clinical signs/skin areas most commonly impacted in Arabian fading syndrome
White splotches are on the face, especially the bridge of the muzzle or around the eyes. Color loss may wax and wane.
61
another names for alpha-MSH
Melanocortin
62
What type of UV rays are primarily responsible for carcinogenesis via direct damage to skin cell DNA?
Ultraviolet B (UVB) rays *UVA is indirectly involved due to free radical production
63
The Merle coat phenotype is assocaited with a mutation in what gene?
SILV
64
Harlequin coat patterns in Great Danes are associated with mutations in what gene?
PSMB7
65
Deficiency in what dietary amino acids can lead to decreased melanin synthesis?
Phenylalanine (red-brown coloration instead of black) and Tyrosine (coat greying)
66
Disorders of melanosome transfer
- Lavendar foal syndrome in Arabian foals - Color dilution alopecia (assocaited in part with MLPH mutation)
67
Rat Tail syndrome in cattle cause what?
hypotrichosis with coat-color dilution
68
Rat Tail Syndrome in cattle is caused by a mutation in what genes?
PMEL & MC1R
69
Leopard spotting complex + congenital stationary night blindness in horses (mostly Apaloosas) is caused by a defect in what gene?
TRPM1
70
Histologic findings in leukocytoclastic vasculitis?
- Intramural inflammation (visualized as inflammatory cells transmigrating the vessel histologically) - endothelial cell swelling - leukocytoclasia - hemorrhage, and fibrinoid necrosis of the vessel wall
71
Main inflammatory cell in the majority of cases of leukocytoclastic vasculitis
Neutrophils (eos or lymphs also seen in some cases)
72
Horses with leukocytoclastic vasculitis are most often affected over what areas? Clinical signs?
- Un-pigmented areas of distal limbs (pastern) - crusting and exudate
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