排序方式: 共有49条查询结果,搜索用时 15 毫秒
31.
Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways 总被引:21,自引:0,他引:21
Simons M Gloy J Ganner A Bullerkotte A Bashkurov M Krönig C Schermer B Benzing T Cabello OA Jenny A Mlodzik M Polok B Driever W Obara T Walz G 《Nature genetics》2005,37(5):537-543
Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development. 相似文献
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Production of pharmaceutical proteins in milk 总被引:2,自引:0,他引:2
I Wilmut A L Archibald M McClenaghan J P Simons C B Whitelaw A J Clark 《Experientia》1991,47(9):905-912
There is every reason to expect that it will be possible within the next few years to begin to use farm animals to produce large quantities of some of the human proteins that are needed for the treatment of disease. Revolutionary new opportunities for the production of novel proteins in milk have been created by the development of methods for gene transfer. Exploitation of these opportunities depends upon selection and cloning of milk protein genes and identification of the sequences that govern tissue specific hormonally induced expression in the mammary gland. Studies with three genes, ovine beta-lactoglobulin, rat beta-casein and whey acidic protein of rat and mouse, suggest that they may all meet this requirement. Fragments of the ovine beta-lactoglobulin, murine whey acidic protein and rabbit beta-casein genes have directed production of novel proteins in the milk of transgenic mice, sheep, rabbits and pigs. The proteins were biologically active and usually co-migrated with authentic proteins. In early experiments, protein concentration was low, but our recent observations suggest that fusion genes containing genomic clones direct production of concentrations of protein that are suitable for commercial exploitation. In the longer term, two approaches may offer the potential of more reliable expression. Control elements capable of directing expression that is independent of site of insertion of the gene, but dependent on the number of copies of the gene, have been identified for a small number of genes. The availability of such elements for the milk protein genes would increase the reliability of gene expression considerably. Alternatively, targeted mutation of genes may allow the insertion of coding sequences within an existing gene so avoiding position effects. 相似文献
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Zusammenfassung Ein einfacher Apparat ermöglicht mit direkter Röntgenbestrahlung kinematographische Aufnahmen von Tierbewegungen. Der Apparat besteht aus einer Drehscheibe und einer Säule von Zahnröntgenfilmen, welche durch die Scheibe jeweils nach Belichtung entfernt wird. Als Beispiel wurden Fisch-Atmungsbewegungen analysiert. 相似文献
35.
Production of pharmaceutical proteins in milk 总被引:1,自引:0,他引:1
I. Wilmut A. L. Archibald M. McClenaghan J. P. Simons C. B. A. Whitelaw A. J. Clark 《Cellular and molecular life sciences : CMLS》1991,47(9):905-912
There is every reason to expect that it will be possible within the next few years to begin to use farm animals to produce large quantities of some of the human proteins that are needed for the treatment of disease. Revolutionary new opportunities for the production of novel proteins in milk have been created by the development of methods for gene transfer. Exploitation of these opportunities depends upon selection and cloning of milk protein genes and identification of the sequences that govern tissue specific hormonally induced expression in the mammary gland. Studies with three genes, ovine -lactoglobulin, rat -casein and whey acidic protein of rat and mouse, suggest that they may all meet this requirement. Fragments of the ovine -lactoglobulin, murine whey acidic protein and rabbit -casein genes have directed production of novel proteins in the milk of transgenic mice, sheep, rabbits and pigs. The proteins were biologically active and usually co-migrated with authentic proteins. In early experiments, protein concentration was low, but our recent observations suggest that fusion genes containing genomic clones direct production of concentrations of protein that are suitable for commercial exploitation. In the longer term, two approaches may offer the potential of more reliable expression. Control elements capable of directing expression that is independent of site of insertion of the gene, but dependent on the number of copies of the gene, have been identified for a small number of genes. The availability of such elements for the milk protein genes would increase the reliability of gene expression considerably. Alternatively, targeted mutation of genes may allow the insertion of coding sequences within an existing gene so avoiding position effects. 相似文献
36.
According to the current model of adult epidermal homeostasis, skin tissue is maintained by two discrete populations of progenitor cells: self-renewing stem cells; and their progeny, known as transit amplifying cells, which differentiate after several rounds of cell division. By making use of inducible genetic labelling, we have tracked the fate of a representative sample of progenitor cells in mouse tail epidermis at single-cell resolution in vivo at time intervals up to one year. Here we show that clone-size distributions are consistent with a new model of homeostasis involving only one type of progenitor cell. These cells are found to undergo both symmetric and asymmetric division at rates that ensure epidermal homeostasis. The results raise important questions about the potential role of stem cells on tissue maintenance in vivo. 相似文献
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Deepak Atri Bruno Larrivée Anne Eichmann Michael Simons 《Cellular and molecular life sciences : CMLS》2014,71(5):867-883
Arteriovenous malformations occur when abnormalities of vascular patterning result in the flow of blood from arteries to veins without an intervening capillary bed. Recent work has revealed the importance of the Notch and TGF-β signaling pathways in vascular patterning. Specifically, Notch signaling has an increasingly apparent role in arterial specification and suppression of branching, whereas TGF-β is implicated in vascular smooth muscle development and remodeling under angiogenic stimuli. These physiologic roles, consequently, have implicated both pathways in the pathogenesis of arteriovenous malformation. In this review, we summarize the studies of endothelial signaling that contribute to arteriovenous malformation and the roles of genes implicated in their pathogenesis. We further discuss how endothelial signaling may contribute to vascular smooth muscle development and how knowledge of signaling pathways may provide us targets for medical therapy in these vascular lesions. 相似文献
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1998年9月3日瑞士航空公司第111航班飞机失事,遇难乘客229人,世界著名细胞学家汤马斯·克列斯也名列其中。他年方46岁,正当生命和事业的高峰──他刚刚成为父亲,刚被任命为日内瓦大学生物系主任。克列斯在本世纪对年代进入细胞生物学领域,正值这一学科发生迅速变化之时。此前,该学科主要从事细胞和组织的形态学描述。随着分子生物学的产生,少数有影响的生物学家开创了研究细胞组织的分子机制的工作,以求解答这样的问题:每个细胞制造的成千蛋白质是如何找到它们在细胞间与细胞外的正确去处的?为了研究由细胞质中的蛋白质工厂所合成… 相似文献
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Polarized sorting of glypiated proteins in hippocampal neurons. 总被引:14,自引:0,他引:14
Our recent studies suggested that neurons and epithelial cells sort viral glycoproteins in a similar manner. The apical influenza virus haemagglutinin was preferentially delivered to the axon of hippocampal neurons in culture, whereas the basolateral vesicular stomatitis virus glycoprotein was sorted to the dendrites. To investigate whether other membrane proteins showed similar sorting in neurons and epithelial cells, we have analysed the localization of a glypiated (glycosylphosphatidylinositol anchored) protein, Thy-1, in hippocampal neurons in culture. In MDCK and other epithelial cells, endogenous glycosylphosphatidylinositol (GPI)-anchored proteins, as well as mutated exogenous proteins containing the GPI-attachment signal, undergo preferential delivery to the apical surface. This polarized sorting of GPI-anchored proteins has been proposed to occur by the same mechanisms as the sorting of glycolipids to the apical surface. We report here that the neuronal GPI-protein Thy-1 is present in hippocampal neurons in culture and is exclusively located on the axonal surface. This finding further strengthens our hypothesis that the mechanisms of sorting of surface components may be similar in neurons and epithelial cells. 相似文献
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