成黑色素细胞生成过程中信号调节的研究进展

动物体内的黑色素细胞合成了黑色素从而决定其肤色和毛色。全身各处的黑色素细胞有2种来源:①由神经管上皮细胞分化而来的视网膜色素上皮细胞;②由神经嵴细胞在胚胎发育早期分化为成黑色素细胞进而发育成熟为黑色素细胞从而行使其功能。通过对小鼠和人类的发育遗传学研究,结果表明神经嵴细胞衍生的黑色素细胞的发育分化是一个非常复杂的过程,受到多重信号因子的调控。其中影响黑色素细胞发育过程的转录因子有SOX10、MITF和PAX3,信号通路有KIT及其配体KITL信号通路、WNT/β-catenin信号通路、EDN3及其受体EDNRB信号通路。MITF被认为是黑色素细胞发育过程中非常关键的调控因子,而3条通路也被认为与神经嵴细胞来源的黑色素细胞的发育有极为密切的关系且能调节MITF功能及其活性。作者总结了这个领域的研究进展并指出早期神经嵴细胞的发育调控可能是乌骨鸡和乌骨绵羊乌质性状形成的根本原因。     

黑色素形成调控机理及乌骨绵羊黑色素沉积候选基因研究进展

黑色素(melanin)产生于黑色素细胞,是由酚类或吲哚类物质氧化聚合而成的不易溶于水的聚合体,广泛存在于微生物和动植物机体,具有消除自由基、抗氧化、抑制病毒感染、激活免疫系统、提高机体免疫力、延缓衰老等生理功能。酪氨酸在酪氨酸酶作用下生成多巴,多巴经过系列复杂的生物学反应形成黑色素。现有研究发现,多种信号通路(α-MSH/MC1R/cAMP信号通路、Wnt/β-catenin信号通路、PI3K/Akt/GSK3β信号通路、MAPK信号通路等)及相关调控因子(MITF、MC1R、TYR等)参与了黑色素的形成过程。一般认为,哺乳动物黑色素细胞主要分布于皮肤和毛囊组织,而乌骨绵羊的内脏组织也能存在大量黑色素细胞,其形成机制尚不明确。乌骨绵羊的乌质性状是重要的经济性状,与其营养和药用价值密切相关,受机体组织黑色素沉积程度的影响。文章简述了黑色素的理化性质、生物功能及其合成路径,回顾了近年来发现的调控动物机体黑色素合成的信号通路及其作用机理,总结了影响乌骨绵羊黑色素沉积和分布规律相关候选功能基因的研究现状,以期为深入研究黑色素沉积调控机理及候选功能基因应用于生产实践提供参考。     

黑色素细胞调控小眼畸形相关转录因子的研究进展

黑色素细胞的主要功能是合成黑色素。黑色素是皮肤受紫外线照射后"自我保护"形成的产物,在黑色素细胞的亚细胞器—黑素小体中合成。黑色素的形成过程受到了许多基因的调控,其中小眼畸形相关转录因子(MITF)对黑色素细胞发育、增殖和存活至关重要。本文首先对MITF基因的结构和功能进行介绍,其次对MITF参与的相关分子信号通路,以及MITF在黑色素细胞的生长发育、黑色素的合成的影响进行综述,最后概述了MITF在人类中的突变影响,并对未来的研究方向进行展望。有助于探明哺乳动物黑色素的合成的分子机制,为哺乳动物毛色的形成提供理论依据。     

黑色素细胞中MITF相关信号通路调控因子的研究进展

小眼畸形相关转录因子(MITF)是一种含有碱性螺旋-环-螺旋亮氨酸拉链结构的转录因子,它是黑色素细胞色素沉积的主要调节因子。MITF基因的突变会引起黑色素细胞产生缺陷,进而产生一些与黑色素相关的疾病,更有甚者会引起恶性肿瘤。了解MITF的分子机制及其相关通路将为这些疾病治疗方法提供线索。MITF参与黑色素细胞的分化、生长和存活,涉及多种信号通路。许多生长因子信号通路也参与MITF在蛋白质与启动子水平上的调节。本文总结了几种在黑色素细胞中MITF相关生长因子的信号通路。     

α-黑素细胞刺激素对泰和乌骨鸡皮肤黑色素细胞增殖及黑色素合成的影响

旨在研究α-黑色素细胞刺激素(α-melanocyte stimulating hormone,α-MSH)对泰和乌骨鸡皮肤黑色素细胞增殖和黑色素生成的影响,初步探讨α-MSH调控泰和乌骨鸡黑色素合成的机制。利用体外培养的乌骨鸡皮肤黑色素细胞,观察不同质量浓度α-MSH(0、2.5、5、10 mg/L)及其拮抗剂([D-Trp7,Ala8,D-Phe10]α-MSH(6-11)-amide,D-AD-MSH)处理后黑色素细胞增殖、黑素皮质素受体1(melanocortin 1receptor,MC1R)基因表达、酪氨酸酶(tyrosinase,TYR)活性、环磷酸腺苷(cyclic adenosine monophosphate,cAMP)含量和黑色素含量的变化。结果表明,不同质量浓度的α-MSH对细胞有促增殖的作用,2.5mg/Lα-MSH处理组细胞的增殖率极显著高于不添加α-MSH的对照组(P0.01)。α-MSH剂量依赖性地提高MC1R基因表达。2.5mg/Lα-MSH处理组细胞cAMP的含量显著高于对照组(P0.05),其他处理组之间差异不显著(P0.05)。不同浓度的α-MSH处理均极显著提高细胞TYR活性(P0.01或P0.05)。与对照组相比,2.5mg/Lα-MSH极显著提高皮肤黑色素细胞的黑色素含量(P0.01),5、10.0mg/Lα-MSH具有提高黑色素细胞黑色素含量的趋势(P0.05)。α-MSH拮抗剂D-A-D-MSH预处理乌骨鸡皮肤黑色素细胞显著抑制α-MSH对黑色素细胞MC1R基因表达、cAMP含量、TYR活性和黑色素含量的上调作用(P0.05)。α-MSH能促进泰和乌骨鸡皮肤黑色素细胞增殖,提高MC1R基因表达、cAMP含量以及TYR活性并进而促进黑色素合成。     

酪氨酸酶转运对黑色素生成影响研究进展

哺乳动物毛色的形成依赖于黑色素细胞中黑色素数量及分布比例,酪氨酸酶类(TYR/TYRP1)的转运及其活性是黑色素合成的关键。衔接蛋白(AP-1/3)和溶酶体相关细胞器生物合成复合物(BLOC-1,2,3)将TYR/TYRP1从早期核内体转运至黑素小体,若TYR/TYRP1无法转运至黑素小体中,黑色素合成则会受到抑制。ATP7A将铜离子转移到TYR/TYRP1,从而激活TYR/TYRP1活性,ATP7A的减少同样会使黑色素细胞中黑色素合成量减少。关注这些复合物在转运TYR/TYRP1的作用及影响其活性的因素,可以从不同的角度解析黑色素合成机理,以此为基础探索哺乳动物毛色的淡化机制,以期为阐明人类黑色素合成障碍的相关疾病提供理论依据。     

小鼠黑色素细胞沉默及过表达色素上皮衍生因子对黑色素合成的影响

旨在研究色素上皮衍生因子(pigment epithelium-derived factor, PEDF)与黑色素合成调控因子之间的互作关系，探索PEDF对黑色素细胞活力和黑色素合成的调控作用，为研究动物毛色形成机制提供基础。本研究将PEDF siRNA及PEDF过表达载体分别转染小鼠黑色素细胞，对黑色素细胞活力、黑色素含量进行检测，采用qRT-PCR、Western blotting及细胞免疫荧光对PEDF、Wnt1、Wnt3α、MITF和β-catenin的表达和定位进行检测。黑色素细胞PEDF沉默后，黑色素细胞的细胞活力增强，黑色素含量增加，Wnt1、Wnt3α、MITF和β-catenin的mRNA和蛋白表达量升高；黑色素细胞PEDF过表达后，黑色素细胞活力减弱，黑色素含量减少，Wnt1、Wnt3α、MITF和β-catenin的mRNA和蛋白表达量降低。细胞免疫荧光结果显示：PEDF、Wnt1、MITF、β-catenin表达于黑色素细胞的细胞质；Wnt3α表达于黑色素细胞的细胞质和细胞膜。本研究证实：PEDF使黑色素细胞活力减弱，可通过下调促黑色素生成相关的因子Wnt1、W...     

TYR基因及其与动物毛色关系的研究进展

毛色是毛皮动物重要的品种特征之一,是一种易于观察的表型性状。黑色素对动物毛色的形成起至关重要的作用。在动物体内酪氨酸在酪氨酸酶(TYR)的催化作用下,经由DOPA、多巴醌、吲哚醌等形式最后生成黑色素。动物毛色的形成主要与黑色素细胞中合成的两种色素(真黑色素、褐黑色素)比例有关。黑色素细胞中色素的合成受多个基因和信号通路调控。动物毛色之所以具有多样性,也是由于这些基因调控所致。在众多的调控基因中,其中目前研究较多的主要有黑素皮质素受体1(MC1R)、剌鼠信号蛋白基因(ASIP)、TYR家族(TYR、TYRP1、TYRP2)等,各基因间相互作用形成不同的毛色。文章简要介绍黑色素形成的机理及概况,重点对TYR基因结构和功能及其在多种动物毛色方面的研究现状进行综述,以便为动物毛色选育提供理论依据。     

家畜毛色形成分子基础及应用研究进展

动物毛色是一种容易被识别的表型,也可作为筛查某些疾病的有效手段。毛色主要由黑色素细胞产生的真黑色素和棕黑色素的分布、比例和产生速率所决定。许多基因对黑色素的产生和分布起着重要调控作用,各基因间的不同基因型形成多种基本毛色、淡化毛色和花斑。此外,miRNA靶向结合毛色主效基因mRNA,诱导抑制/增强其转录翻译过程,从而调控毛色基因的表达,影响黑色素合成。文章简述了家畜调控毛色的主效基因黑色素皮质素受体1（MC1R）、野灰位点信号蛋白（ASIP）、原癌基因（KIT）、酪氨酸酶关联蛋白（TYRP）、小眼畸形相关转录因子（MITF）和内皮素受体B（EDNRB）的DNA序列多态性（不同基因型）与毛色性状、疾病之间的关系;介绍了毛色形成相关miRNA挖掘鉴定、miRNA调控毛色相关基因研究进展与毛色基因研究应用价值,旨在为今后研究家畜毛色机理提供理论依据。     

The biology of melanocytes

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.     

Pigmentation of the aortic and pulmonary valves in C57BL/6J x Balb/cByJ hybrid mice of different coat colours

Neural crest‐derived melanocytes have been recorded in several parts of the mammalian heart but not in the pulmonary valve. We report here the presence of melanin‐containing cells in the leaflets (cusps) of both the aortic and pulmonary valves. A total of 158 C57BL/6J x Balb/cByJ hybrid mice exhibiting four coat colours, namely black, white, agouti and non‐agouti brown, were examined. We sought for any relationship between the presence of melanocytes in the valves and the coat colour of the animals. The pigmentation levels of the leaflets were accomplished using a scale of five pigment intensities. White mice lacked pigment in the heart. In 10.5% of the remaining animals, there were melanocytes in the pulmonary valve leaflets. Thus, this is the first study to report the presence of such cells in the pulmonary valve of mammals. Melanocytes occurred in the leaflets of the aortic valves of 87.2% of mice. The incidence of melanocytes and the pigmentation level of the leaflets did not statistically differ according to the coat colours of the animals. This disagrees with previous observations, indicating that the amount of melanocytes in the heart reflects that of the skin. The incidence and distribution of melanocytes in aortic and pulmonary valves are consistent with the notion that the formation of the arterial valves is mediated by specific subpopulations of neural crest cells. We hypothesize that melanocytes, even not producing melanin, may be more frequent in the heart than previously thought, exerting presumably an immunological function.     

动物黑色素细胞及其相关性状形成机制的研究进展

黑色素细胞是合成黑色素的细胞，由其前体细胞黑色素母细胞分化而来，胚胎期黑色素母细胞的形成有两次，一次是具有黑色素细胞特性的神经嵴细胞沿背外侧迁移而形成，另一次是由沿腹侧迁移的神经嵴细胞亚细胞雪旺氏细胞前体（Schwann cell precursors，SCPs）受到某种信号诱导后形成，这是皮肤中黑色素细胞形成的主要方式。黑色素细胞的形成与动物毛发颜色及其他重要经济性状密切相关，其形成的增多或减少，异位形成或异位侵袭均可能导致相应的疾病，但脊椎动物中具有典型黑色素细胞异位形成特征的乌骨鸡却繁衍至今，而且是重要的食用和药用经济动物。探索黑色素细胞的形成及其对相关性状的影响不但能为动物经济性状育种提供相关理论基础，也可为相关疾病的治疗提供理论依据。作者从黑色素细胞的来源及其形成过程中参与的信号因子来探讨其形成机制，并对黑色素细胞相关性状的形成机制尤其是乌质性状进行综述。     

Black hair follicular dysplasia in Large Münsterländer dogs: clinical, histological and ultrastructural features

Four Large Münsterländer cross‐bred dogs affected with black hair follicular dysplasia (BHFD) and one unaffected control littermate were observed, and skin was sampled weekly over the first 19 weeks of life. Affected dogs were born with silvery grey hair, a consequence of melanin clumping in the hair shafts. Hair bulb melanocytes were densely pigmented, and contained abundant stage IV melanosomes but adjacent matrix keratinocytes lacked melanosomes. Melanin clumping was not prominent in epidermal melanocytes in the haired skin but occurred in the foot pads. Follicular changes progressed from bulbar clumping, clumping in the isthmus/infundibulum and finally to dysplastic hair shafts. Alopecia developed progressively in pigmented areas. Silver‐grey hair, melanin clumping, accumulation of stage IV melanosomes within melanocytes and insufficient melanin transfer to adjacent keratinocytes are also classic features of human Griscelli syndrome. The underlying cause in Griscelli syndrome is a defect of melanocytic intracellular transport proteins leading to inadequate and disorganized melanosome transfer to keratinocytes with resultant melanin clumping. In view of the correlation in the phenotype, histology and ultrastructure between both disorders, a defect in intracellular melanosome transport is postulated as the pathogenic mechanism in BHFD.     

The influence of aging and low zinc nutrition on the choroid in the pig: I. The melanocyte

The effects of low zinc nutrition and aging on central choroidal melanocytes were examined in the pig. Three populations of pigs (young, pregnant and aged), were maintained on either control (C) or low zinc (LZ) diets. Twenty-five weanling boars were sacrificed at 2, 4, 8, 10, and 12-month intervals, and nine pregnant sows and eight aged sows were sacrificed after a 6-month interval. Melanocytes of the central choroid were morphologically and morphometrically examined. The melanocyte was found to be conservative in its form, which was mostly elliptical longitudinal profile, throughout the different age populations that were fed the C diet. Morphometric observations revealed that this cell type increased in size in the oldest animals, having been 40% greater than that in the younger two populations. However, the overall percentage area occupied by melanocytes remained the same throughout all age groups. In the animals that were fed the LZ diets, a large subpopulation of choroidal melanocytes was oval to round in shape in the pregnant and aged groups. Many members of this subpopulation possessed less opaque pigment than the elliptically shaped cell. Measurements of the size and percentage area occupied in these oldest groups increased significantly. In addition to the change of size, shape and melanin opaqueness, unusually large melanosomes were consistently observed in the pregnant and aged LZ groups. Low zinc nutrition had a remarkable age-related impact on the usually quiescent melanocyte.     

Molecular characteristics and site specific distribution of the pigment of the silky fowl

Silky fowl, a breed of chicken, is hyperpigmented in its various internal tissues. The pigment was extracted from various tissues of two strains of Silky fowl to determine its molecular structure and internal distribution. Analysis by infrared spectroscopy showed two spectrum patterns of the pigment in Silky fowl; one is from ovary and testis, the other is from periosteum and feather. The difference between the two spectra is possibly due to the sulfur contents of melanin. Especially, the spectra of the pigments from feather and periosteum shared the characteristics of synthesized melanin spectrum in common, which indicates that the melanocytes dispersed in these tissues were functionally the same. According to our quantitative analysis, the tissues examined were classified significantly in the order of the pigment content (p<0.05): periosteum > gonads (ovary or testis) = trachea > or = heart, liver, gizzard, cecum, muscles (Pectoralis and Supracoracoideus) and skin. In addition, the specific regions of embryonic neural crest derived cells, such as cardiac artery and various parts of cephalic tissues, were found to be locally hyperpigmented. These data suggest that hyperpigmentation (fibromelanosis) in Silky fowl chicken occurs in a tissue- and organ-specific manner, which is strongly related to neural crest cell development. It is hypothesized that neural crest cells of the bird, containing melanocyte progenitors, acquire unusual ability to differentiate into melanocytes excessively, and to extend the distribution of their descendant along the destinations of neural crest derivatives.