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A Martin R Papa NJ Nadeau RI Hill BA Counterman G Halder CD Jiggins MR Kronforst AD Long WO McMillan RD Reed 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(31):12632-12637
Although animals display a rich variety of shapes and patterns, the genetic changes that explain how complex forms arise are still unclear. Here we take advantage of the extensive diversity of Heliconius butterflies to identify a gene that causes adaptive variation of black wing patterns within and between species. Linkage mapping in two species groups, gene-expression analysis in seven species, and pharmacological treatments all indicate that cis-regulatory evolution of the WntA ligand underpins discrete changes in color pattern features across the Heliconius genus. These results illustrate how the direct modulation of morphogen sources can generate a wide array of unique morphologies, thus providing a link between natural genetic variation, pattern formation, and adaptation. 相似文献
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Central nervous system microglia promote neuronal regeneration and sequester toxic β-amyloid (Aβ) deposition during Alzheimer's disease. We show that the cytokine erythropoietin (EPO) decreases the toxic effect of Aβ on microgliain vitro. EPO up-regulates the cysteine-rich glycosylated wingless protein Wnt1 and activates the PI 3-K/Akt1/mTOR/ p70S6K pathway. This in turn increases phosphorylation and cytosol trafficking of Bad, reduces the Bad/Bcl-xL complex and increases the Bcl-xL/Bax complex, thus preventing caspase 1 and caspase 3 activation and apoptosis. Our data may foster development of novel strategies to use cytoprotectants such as EPO for Alzheimer's disease and other degenerative disorders. 相似文献
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van der Horst PH Wang Y van der Zee M Burger CW Blok LJ 《Molecular and cellular endocrinology》2012,358(2):176-184
Wnt/β-catenin signalling plays a rate-limiting role in early development of many different organs in a broad spectrum of organisms. In the developing Müllerian duct, Wnt/β-catenin signalling is important for initiation, outgrowth, patterning and differentiation into vagina, cervix, uterus and oviducts. In adult life, sex hormones modulate Wnt/β-catenin signalling in the endometrium to maintain the monthly balance between estrogen-induced proliferation and progesterone-induced differentiation, and enhanced Wnt/β-catenin signalling seems to be involved in endometrial carcinogenesis. However, early in pregnancy enhanced Wnt/β-catenin signalling is prerequisite for proper implantation and invasion of trophoblast cells into endometrium and myometrium thus helping to form a placenta. Overall, it seems that tight control of Wnt/β-catenin signalling in time and space is important for initiation, development and normal function of the female reproductive tract. However, if Wnt/β-catenin signalling is not kept in check, it easily seems to initiate or contribute to development of a number of uterine disorders. 相似文献
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We investigated the role of the Wnt signaling pathway in cerebral ischemia/reperfusion injury by examining β-catenin and glycogen synthase kinase-3β protein expression in the rat hippocampal CA1 region following acute cerebral ischemia/reperfusion. Our results demonstrate that cell apoptosis increases in the CA1 region following ischemia/reperfusion. In addition, β-catenin and glycogen synthase kinase-3β protein expression gradually increases, peaking at 48 hours following reperfusion. Dickkopf-1 administration, after cerebral ischemia/reperfusion injury, results in decreased cell apoptosis, and β-catenin and glycogen synthase kinase-3β expression, in the CA1 region. This suggests that β-catenin and glycogen synthase kinase-3β, both components of the Wnt signaling pathway, participate in cell apoptosis following cerebral ischemia/reperfusion injury. 相似文献
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目的 研究无翅型MMTV整合位点家族成员3(wingless-type MMTV integration site family,member 3,Wnt3)在大鼠体内外牙囊中的表达,检测成骨诱导后Wnt3在大鼠牙囊细胞中的表达变化,探讨Wnt3在牙囊成骨分化中的作用.方法 取出生后1、3、5、7、9、11、13 d的SD仔鼠各1只,引颈处死,切取下颌骨,取出生后各时间点的组织切片各3张作为实验组,阴性对照组以磷酸盐缓冲液代替一抗,滴加在出生后11d的组织切片上,其余处理同实验组.免疫组化检测Wnt3在大鼠体内牙囊中的表达.间接免疫荧光检测Wnt3在牙囊细胞内的表达和分布.茜素红染色检测成骨诱导后矿化结节的形成.蛋白质印迹法检测成骨诱导1、2、3周后牙囊细胞中Wnt3和β-联蛋白(β-catenin)表达的变化.结果 Wnt3在出生后第1、3天的大鼠牙囊组织内无明显表达,第5天开始出现阳性表达,并持续表达至第13天.免疫荧光检测显示Wnt3在牙囊细胞胞质中表达.成骨诱导后牙囊细胞分化为成骨细胞,形成矿化结节,茜素红染色阳性.成骨诱导第1周Wnt3蛋白表达(2.60±0.04)较阴性对照组(1.00±0.00)显著增加(P<0.05),并随着诱导时间的延长Wnt3表达逐渐减少,至第3周Wnt3在成骨诱导组表达水平(1.00±0.05)与阴性对照组基本相等,差异无统计学意义(P>0.05).β-联蛋白在成骨诱导1、2、3周后表达增加(分别为1.95±0.05、9.77 ±0.65、1.75±0.21),与阴性对照组(1.00 ±0.00)相比差异均有统计学意义(P<0.05),并在第2周达峰值(9.77±0.65),后逐渐降低.结论 Wnt3在体内外大鼠牙囊中表达,成骨诱导早期牙囊细胞中Wnt3表达明显增加,提示Wnt3可能参与牙囊细胞的早期成骨向分化;Wnt3和β-联蛋白在成骨诱导过程中表达水平的差异提示Wnt3可能与其他因子或信号通路成分相互作用,调控β-联蛋白的表达,参与牙囊细胞的成骨向分化. 相似文献
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