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Tomohisa Hirobe, Tatako Shibata, Kiyoshi Sato
BACKGROUND: Oxidative stress caused by hydrogen peroxide (H2O2) elicits harmful effects on human melanocytes such as DNA damage and cell death. On the contrary, H2O2 is known to possess beneficial effects on melanocytes. However, mechanisms of the beneficial effects of H2O2 on melanocytes have not been fully understood, especially the indirect effects on melanocyte proliferation and differentiation from cells constituting surrounding tissue environment such as fibroblasts. OBJECTIVE: The aim of this study was to clarify whether H2O2-treated human fibroblasts affect the proliferation and differentiation of human melanocytes using serum-free co-culture system...
September 5, 2016: Journal of Dermatological Science
Joanna Birch, Cassie J Clarke, Andrew D Campbell, Kirsteen Campbell, Louise Mitchell, Dritan Liko, Gabriela Kalna, Douglas Strathdee, Owen J Sansom, Matthew Neilson, Karen Blyth, Jim C Norman
The cell's repertoire of transfer RNAs (tRNAs) has been linked to cancer. Recently, the level of the initiator methionine tRNA (tRNAi(Met)) in stromal fibroblasts has been shown to influence extracellular matrix (ECM) secretion to drive tumour growth and angiogenesis. Here we show that increased tRNAi(Met) within cancer cells does not influence tumour growth, but drives cell migration and invasion via a mechanism that is independent from ECM synthesis and dependent on α5β1 integrin and levels of the translation initiation ternary complex...
October 15, 2016: Biology Open
Motoki Nakamura, Emi Nishida, Akimichi Morita
The aryl hydrocarbon receptor (AHR) mediates melanocyte activation and skin tanning. We hypothesized that the AHR also mediates melanoblast-to-melanocyte maturation. In a cloned cell line, NCCmelb4, derived from mouse neural crest cells, we investigated AHR expression in melanoblasts stimulated by UV irradiation and AHR agonists. We irradiated the cells with UV, ranging from 280 to 380 nm in 10-nm increments, using a multiwavelength irradiation spectral apparatus. Tyrosinase expression significantly increased with bimodal peaks at 310 and 360 nm...
August 2016: Experimental Dermatology
Weiming Qiu, Hui Tang, Haiying Guo, Mingxing Lei, Hongtao Yan, Xiaohua Lian, Jinjin Wu
Melanocyte stem cells (McSCs) undergo cyclical activation and quiescence together with hair follicle stem cells (HFSCs). This process is strictly controlled by the autonomous and extrinsic signaling environment. However, the modulation of factors important for the activation of McSCs for hair pigmentation remains unclear. 12-O-tetradecanoylphorbol-13-acetate (TPA) mimics vital signaling pathways involved in melanocyte growth and melanogenesis in vitro. To investigate whether TPA regulates quiescent McSCs for hair pigmentation, we topically smeared TPA on 7-week-old mouse dorsal skin and found that TPA stimulated hair growth and hair matrix pigmentation...
July 27, 2016: Cell and Tissue Research
Haoyuan Han, Chunchun Mao, Ningbo Chen, Xianyong Lan, Hong Chen, Chuzhao Lei, Ruihua Dang
Kit gene is a genetic determinant of horse white coat color which has been a highly valued trait in horses for at least 2,000 years. Single nucleotide polymorphisms (SNPs) in Kit are of importance due to their strong associations with melanoblast survival during embryonic development. In this study, a mutation analysis of all 21 Kit exons in 14 Chinese domestic horse breeds revealed six SNPs (g.91214T>G, g.143245T>G, g.164297C>T, g.170189C>T, g.171356C>G, and g.171471G>A), which located in 5'-UTR region, intron 6, exon 15, exon 20, intron 20, and exon 21 of the equine Kit gene, respectively...
February 2016: Japanese Journal of Veterinary Research
Tomohisa Hirobe, Tatako Shibata, Rumiko Fujiwara, Kiyoshi Sato
BACKGROUND: Although many kinds of keratinocyte-derived factors are known to regulate the proliferation and differentiation of human melanocytes, it is not well defined whether dermis-derived factors work in a similar way. OBJECTIVE: The aim of this study is to clarify whether dermal factors are involved in regulating the proliferation and differentiation of human melanocytes. METHODS: Human epidermal melanoblasts were cultured serially in a serum-free growth medium...
September 2016: Journal of Dermatological Science
Valérie Petit, Lionel Larue
Melanocytes arise from the fourth embryonic layer, the neural crest. They emerge from the roof plate of the neural tube and migrate throughout the body. In mammals, these cells have the capacity to migrate in any type of environment and use various pathways and mechanisms to colonize the skin and hair, and for their maintenance throughout the life of the animal.
September 2016: Experimental Dermatology
Christoph Schwab, Werner Wackernagel, Petra Grinninger, Christoph Mayer, Katharina Schwab, Gerald Langmann, Erika Richtig, Andreas Wedrich, Rainer Hofmann-Wellenhof, Iris Zalaudek
Pigmented cells are derived from neural crest cells, which migrate along the peripheral nerve sheets into their specific final region. During their migration, cells progressively acquire pigment-producing capabilities, maturation, and the shape of melanocytes. These insights, along with specific clinical characteristics of melanocytic nevi, have led to new concepts of cutaneous, periocular, and iris nevogenesis. To further elucidate the specific ocular embryogenic melanoblast distribution and dissemination - that could explain the distinct distribution of uveal melanocytic neoplasms - we investigated the ocular pigmentation of dogs affected by a specific mutation called Merle, which results in either pigment- (wild type) or non-pigment- (mutated type) producing cells...
2016: Cells, Tissues, Organs
Kazuhisa Takeda, Hiroki Hozumi, Koji Ohba, Hiroaki Yamamoto, Shigeki Shibahara
Microphthalmia-associated transcription factor (Mitf) is a key regulator for differentiation of melanoblasts, precursors to melanocytes. The mouse homozygous for the black-eyed white (Mitfmi-bw) allele is characterized by the white-coat color and deafness with black eyes due to the lack of melanocytes. The Mitfmi-bw allele carries LINE-1, a retrotransposable element, which results in the Mitf deficiency. Here, we have established the black spotting mouse that was spontaneously arisen from the homozygous Mitfmi-bw mouse lacking melanocytes...
2016: PloS One
Malkiel A Cohen, Katherine J Wert, Johanna Goldmann, Styliani Markoulaki, Yosef Buganim, Dongdong Fu, Rudolf Jaenisch
The neural crest (NC) represents multipotent cells that arise at the interphase between ectoderm and prospective epidermis of the neurulating embryo. The NC has major clinical relevance because it is involved in both inherited and acquired developmental abnormalities. The aim of this study was to establish an experimental platform that would allow for the integration of human NC cells (hNCCs) into the gastrulating mouse embryo. NCCs were derived from pluripotent mouse, rat, and human cells and microinjected into embryonic-day-8...
February 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
Natsuki Watanabe, Tsutomu Motohashi, Masahiro Nishioka, Norito Kawamura, Tomohisa Hirobe, Takahiro Kunisada
BACKGROUND: Melanoblasts (MBs), derived from neural crest cells, only differentiate into melanocytes (Ms) in vivo. We previously showed that MBs isolated from mouse skin were multipotent, generating neurons (Ns) and glial cells (Gs) together with Ms. Using Sox10-IRES-Venus mice and mouse embryonic stem cells, we investigated how MBs expressed their multipotency. RESULTS: MBs generated colonies containing Ns, Gs, and Ms in the presence of ST2 stromal cells, but they generated only M colonies when incubated with keratinocytes or ST2 culture supernatant, thus showing that MBs required contact with ST2 stromal cells for expression of their multipotency...
April 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
John E Harris
Melanocytes in patients with vitiligo possess intrinsic abnormalities that contribute to its pathogenesis. Regazzetti et al. report that CXCL10 expression reflects subtle inflammation in normal-appearing skin but not in stable depigmented lesions, supporting the hypothesis that melanocytes themselves initiate autoimmune inflammation prior to clinically evident disease. In addition, they find that oxidative stress in melanocytes impairs WNT signaling and that targeting this pathway induces melanoblast differentiation...
December 2015: Journal of Investigative Dermatology
M Böhm
Hypomelanoses of the skin encompass a wide spectrum of congenital and acquired alterations in melanin pigmentation. These diseases can be localized or universal. The pathobiology of cutaneous hypomelanoses is heterogeneous and includes defects in melanoblast migration from the neural crest to the epidermis, alterations in melanogenesis and melanin transfer to keratinocytes, and destruction of pigment cells by autoimmune and inflammatory processes. Importantly, some congenital forms of universal hypomelanoses are associated with involvement of internal organs (e...
December 2015: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
L Pan, X Ma, B Wen, Z Su, X Zheng, Y Liu, H Li, Y Chen, J Wang, F Lu, J Qu, L Hou
OBJECTIVES: Control of cell proliferation is critical for accurate cell differentiation and tissue formation, during development and regeneration. Here, we have analysed the role of microphthalmia-associated transcription factor MITF and its direct target, T-box factor TBX2, in regulating proliferation of mammalian neural crest-derived melanocytes. MATERIALS AND METHODS: Immunohistochemistry was used to examine spatial and temporal expression of TBX2 in melanocytes in vivo...
December 2015: Cell Proliferation
Tomohisa Hirobe, Akira Ishikawa
BACKGROUND: The mouse pink-eyed dilution (oculocutaneous albinism II; p/Oca2(p)) locus is known to control tyrosinase activity, melanin content, and melanosome development in melanocytes. Pink-eyed dilution castaneus (p(cas)/Oca2(p-cas)) is a novel mutant allele on mouse chromosome 7 that arose spontaneously in Indonesian wild mice, Mus musculus castaneus. Mice homozygous for Oca2(p-cas) usually exhibit pink eyes and beige-colored coat on nonagouti C57BL/6 (B6) background. Recently, a novel spontaneous mutation occurred in the progeny between this mutant and B6 mice...
December 2015: Journal of Dermatological Science
Dana Koludrovic, Patrick Laurette, Thomas Strub, Céline Keime, Madeleine Le Coz, Sebastien Coassolo, Gabrielle Mengus, Lionel Larue, Irwin Davidson
MIcrophthalmia-associated Transcription Factor (MITF) regulates melanocyte and melanoma physiology. We show that MITF associates the NURF chromatin-remodelling factor in melanoma cells. ShRNA-mediated silencing of the NURF subunit BPTF revealed its essential role in several melanoma cell lines and in untransformed melanocytes in vitro. Comparative RNA-seq shows that MITF and BPTF co-regulate overlapping gene expression programs in cell lines in vitro. Somatic and specific inactivation of Bptf in developing murine melanoblasts in vivo shows that Bptf regulates their proliferation, migration and morphology...
October 2015: PLoS Genetics
Pankaj K Agarwalla, Matthew J Koch, Daniel A Mordes, Patrick J Codd, Jean-Valery Coumans
Neurosurgeons encounter a number of pigmented tumors of the central nervous system in a variety of locations, including primary central nervous system melanoma, blue nevus of the spinal cord, and melanotic schwannoma. When examined through the lens of embryology, pigmented lesions share a unifying connection: They occur in structures that are neural crest cell derivatives. Here, we review the important progress made in the embryology of neural crest cells, present 3 cases of pigmented tumors of the nervous system, and discuss these clinical entities in the context of the development of melanoblasts...
January 2016: Neurosurgery
Jennifer D Kubic, Elizabeth C Little, Rebecca S Kaiser, Kacey P Young, Deborah Lang
Several key transcription factors regulate cell growth, survival, and differentiation during neural crest and melanoblast development in the embryo, and these same pathways may be reactivated in tumors arising from the progenitors of these cells. The transcription factors PAX3 and FOXD3 have essential roles in melanoblasts and melanoma. In this study, we define a regulatory pathway where FOXD3 promotes the expression of PAX3. Both factors are expressed in melanoma cells and there is a positive correlation between the transcript levels of PAX3 and FOXD3...
February 2016: Journal of Cellular Biochemistry
Yuanyuan Zhao, Pengchao Wang, Jinzhu Meng, Yuankai Ji, Dongmei Xu, Tianzhi Chen, Ruiwen Fan, Xiuju Yu, Jianbo Yao, Changsheng Dong
MicroRNAs (miRNAs) play an essential role in the regulation of almost all the biological processes, including melanogenesis. MiR-27a-3p is nearly six times higher in white alpaca skin compared to brown skin, which indicates that miR-27a-3p may be a candidate regulator for melanogenesis. Wnt3a plays an important role in promoting melanoblasts to differentiate into melanocytes and melanogenesis. To confirm the function of miR-27a-3p to melanogenesis in mammals, miR-27a-3p mimic, inhibitor and their negative control were transfected into mouse melanocytes...
2015: International Journal of Molecular Sciences
Heidi C E Welch
The P-Rex family are Dbl-type guanine-nucleotide exchange factors for Rac family small G proteins. They are distinguished from other Rac-GEFs through their synergistic mode of activation by the lipid second messenger phosphatidyl inositol (3,4,5) trisphosphate and the Gβγ subunits of heterotrimeric G proteins, thus acting as coincidence detectors for phosphoinositide 3-kinase and G protein coupled receptor signaling. Work in genetically-modified mice has shown that P-Rex1 has physiological importance in the inflammatory response and the migration of melanoblasts during development, whereas P-Rex2 controls the dendrite morphology of cerebellar Purkinje neurons as well as glucose homeostasis in liver and adipose tissue...
2015: Small GTPases
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