共查询到20条相似文献,搜索用时 15 毫秒
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Thompson N Gésina E Scheinert P Bucher P Grapin-Botton A 《Molecular and cellular biology》2012,32(6):1189-1199
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Functional Replacement of the Intracellular Region of the Notch1 Receptor by Epstein-Barr Virus Nuclear Antigen 2 总被引:4,自引:2,他引:2
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Takashi Sakai Yoshihito Taniguchi Kumiko Tamura Shigeru Minoguchi Takataro Fukuhara Lothar J. Strobl Ursula Zimber-Strobl George W. Bornkamm Tasuku Honjo 《Journal of virology》1998,72(7):6034-6039
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Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreas 总被引:8,自引:0,他引:8
Esni F Ghosh B Biankin AV Lin JW Albert MA Yu X MacDonald RJ Civin CI Real FX Pack MA Ball DW Leach SD 《Development (Cambridge, England)》2004,131(17):4213-4224
Notch signaling regulates cell fate decisions in a variety of adult and embryonic tissues, and represents a characteristic feature of exocrine pancreatic cancer. In developing mouse pancreas, targeted inactivation of Notch pathway components has defined a role for Notch in regulating early endocrine differentiation, but has been less informative with respect to a possible role for Notch in regulating subsequent exocrine differentiation events. Here, we show that activated Notch and Notch target genes actively repress completion of an acinar cell differentiation program in developing mouse and zebrafish pancreas. In developing mouse pancreas, the Notch target gene Hes1 is co-expressed with Ptf1-P48 in exocrine precursor cells, but not in differentiated amylase-positive acinar cells. Using lentiviral delivery systems to induce ectopic Notch pathway activation in explant cultures of E10.5 mouse dorsal pancreatic buds, we found that both Hes1 and Notch1-IC repress acinar cell differentiation, but not Ptf1-P48 expression, in a cell-autonomous manner. Ectopic Notch activation also delays acinar cell differentiation in developing zebrafish pancreas. Further evidence of a role for endogenous Notch in regulating exocrine pancreatic differentiation was provided by examination of zebrafish embryos with homozygous mindbomb mutations, in which Notch signaling is disrupted. mindbomb-deficient embryos display accelerated differentiation of exocrine pancreas relative to wild-type clutchmate controls. A similar phenotype was induced by expression of a dominant-negative Suppressor of Hairless [Su(H)] construct, confirming that Notch actively represses acinar cell differentiation during zebrafish pancreatic development. Using transient transfection assays involving a Ptf1-responsive reporter gene, we further demonstrate that Notch and Notch/Su(H) target genes directly inhibit Ptf1 activity, independent of changes in expression of Ptf1 component proteins. These results define a normal inhibitory role for Notch in the regulation of exocrine pancreatic differentiation. 相似文献
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Ptf1a binds to and activates area III, a highly conserved region of the Pdx1 promoter that mediates early pancreas-wide Pdx1 expression 总被引:3,自引:0,他引:3
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Wiebe PO Kormish JD Roper VT Fujitani Y Alston NI Zaret KS Wright CV Stein RW Gannon M 《Molecular and cellular biology》2007,27(11):4093-4104
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