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Milestones in Melanocytes/Melanogenesis
Vincent J. Hearing1
1
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
ARTICLES
Milestone no. 1
Milestone no. 2
Milestone
Milestone
Milestone
Milestone
no.
no.
no.
no.
3
4
5
6
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MELANOCYTES/MELANOGENESIS
Department of Dermatology, Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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HH 22
HH 24
dr
HH 27
2b
MITF+, Sox10+
dm
nt
Sox10+
Isll+
drg
2a
snv
2a
Figure 1. Migratory pathways of chick trunk neural crest cells, adapted from Cell 2009; 139:366379. Region 1: Melanoblasts (Mitf/Sox10 positive cells)
migrating within the dorsolateral pathway (the classic melanoblast migration route). 2a: Melanoblasts located near ventral spinal nerves. 2b: Melanoblasts
along nerves of dorsal rami. nt, neural tube; drg, dorsal root ganglion; dm, dermamyotome; dr, dorsal ramus; snv, ventral branch of the spinal nerve; HH,
Hamburger Hamilton stage.
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CONFLICT OF INTEREST
The authors state no conflict of interest.
REFERENCES
Adameyko I, Lallemend F, Aquino JB et al. (2009)
Schwann cell precursors from nerve innervation
are a cellular origin of melanocytes in skin. Cell
139:36679
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nocyte development, defines a discrete transcription factor family. Genes Dev 8:277080
Nishimura EK, Granter S, Fisher DE (2005)
Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science
307:7204
Nishimura EK, Jordan SA, Oshima H et al. (2002)
Dominant role of the niche in melanocyte stemcell fate determination. Nature 416:85460
Rawles ME (1947) Origin of pigment cells from
neural crest in the mouse embryo. Physiol Zool
20:24870
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MELANOCYTES/MELANOGENESIS
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, USA and
University Park, Pennsylvania, USA
MITF, EDN3
1
ASIP, BCN2, KITLG,
MLPH, RGS19
SLC24A5, MATP,
TYRP1, MYO5A,
DTNBP1, EDA,
OCA2
DCT, EGFR,
DRD2
West
African
East
Asian
4
North
European
ADAM17, DCT,
ADAMTS20, ATRN, MC1R,
LYST, OCA2, EDA, TYRP1
EGFR, DRD2
Figure 1. The evolutionary genetic architecture of skin pigmentation in three populations. Although
gene flow has occurred among human populations, differences in the allele frequencies at pigmentation
genes are observed among. The genes listed have demonstrated signatures of selection as (1) shared
among all humans, (2) shared between East Asian and European populations, (3) unique to East Asian
populations, (4) unique to European populations, and (5) unique to West African populations.
REFERENCES
Chaplin G, Jablonski NG (2010) Human skin
pigmentation as an adaptation to UV radiation.
Proc Natl Acad Sci USA 107:89628
Fuller BB, Spaulding DT, Smith DR (2001)
Regulation of the catalytic activity of preexisting
tyrosinase in black and Caucasian human melanocyte cell cultures. Exp Cell Res 262:197208
Ginger RS, Askew SE, Ogborne RM et al. (2008)
SLC24A5 encodes a trans-Golgi network protein
with potassium-dependent sodium-calcium exchange activity that regulates human epidermal
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Harrison GA, Owen JJT (1964) Studies on the
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Genet Lond 28:2737
Hoggart CL, Parra EJ, Shriver MD et al. (2003)
Control of confounding of genetic associations in
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MELANOCYTES/MELANOGENESIS
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
Tyrosine
Melanosome
TYR
DOPAquinone
Cysteine
TYR
O2
DOPA
CycloDOPA
5SCD or 2SCD
DQ
DOPA
Eumelanin
polymer
CD-quinones
DOPAchrome
Pheomelanin
polymer
DCT
o-Quinoneimine
CO2
DHI
DQ
DHICA
O2
O2
DOPA
1,4-Benzothiazine intermediates
TYR or
TYRP1
Eumelanin
Pheomelanin
Figure 1. Scheme showing the melanogenic pathway that occurs within melanosome, leading to the production of eumelanin and/or pheomelanin.
Abbreviations used are as defined in the text. Adapted from Expert Review of Dermatology 2011;6:97108, with permission from Expert Reviews
(Kondo and Hearing, 2011).
ACKNOWLEDGMENTS
This research was supported in part by the
Intramural Research Program of the NIH, National
Cancer Institute.
REFERENCES
Agrup G, Hansson C, Rorsman H et al. (1979)
Intracellular distribution of DOPA and 5-S-cysteinylDOPA in pigment cells with minimal pigment
formation. Acta Dermatol Venereol Suppl
59:3556
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MELANOCYTES/MELANOGENESIS
those, such as skin biologists or dermatologists, whose interests areprofessionally speakingskin deep, but
included those far-sighted biologists
who recognized that the astonishing
diversity of murine coat color mutants
offered a way to address the general
problem of how genes work. When
technological advances in molecular
genetics made mammalian gene identification almost routine, the resource
of the mouse fancy offered an unrivaled
experimental model system both for
those interested in human pigmentation
and for those whose goals were more
general.
PIGMENT GENES: MENDEL FIRST
REFERENCES
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Duffy DL, Box NF, Chen W et al. (2004)
Interactive effects of MC1R and OCA2 on
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13:44761
Flanagan N, Healy E, Ray A et al. (2000)
Pleiotropic effects of the melanocortin 1 receptor
(MC1R) gene on human pigmentation. Hum Mol
Genet 9:25317
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mice. Am J Pathol
172:124855
NOVEMBER 2011
Karlseder J, Broccoli D, Dai Y et al. (1999) p53and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 283:13215
Khlgatian MK, Eller M, Yaar M et al. (1999)
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Khlgatian MK, Hadshiew IM, Asawanonda P et al.
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Leccia MT, Yaar M, Allen N et al. (2001) Solar
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2729
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Human Medical Genetics Program and Departments of Pediatrics, Biochemistry and Molecular Genetics, and Craniofacial Biology, University of Colorado
School of Medicine, Aurora, Colorado, USA
Correspondence: Richard A. Spritz, E-mail: Richard.Spritz@ucdenver.edu
doi:10.1038/skinbio.2011.7
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