共查询到20条相似文献,搜索用时 15 毫秒
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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 下载免费PDF全文
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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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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The rat elastase I regulatory element is an enhancer that directs correct cell specificity and developmental onset of expression in transgenic mice. 总被引:27,自引:16,他引:11 下载免费PDF全文
R E Hammer G H Swift D M Ornitz C J Quaife R D Palmiter R L Brinster R J MacDonald 《Molecular and cellular biology》1987,7(8):2956-2967
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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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The homeodomain protein PDX1 is required at mid-pancreatic development for the formation of the exocrine pancreas 总被引:5,自引:0,他引:5
Hale MA Kagami H Shi L Holland AM Elsässer HP Hammer RE MacDonald RJ 《Developmental biology》2005,286(1):225-237
The homeoprotein PDX1 is expressed throughout pancreatic development and is thought to play important roles at multiple stages. We describe the properties of a tet-off regulatory scheme to manage the expression of Pdx1 in utero. Cessation of Pdx1 expression at increasingly later gestational times blocked pancreatic development at progressive and morphologically distinct stages and provided the opportunity to assess the requirement for Pdx1 at each stage. Embryonic PDX1 is depleted below effective levels within 1 day of the initiation of doxycycline treatment of pregnant mice. We show that PDX1, which is necessary for early pancreatic development, is also required later for the genesis of acinar tissue, the compartment of the pancreas that produces digestive enzymes. Without PDX1, acini do not form; the precursor epithelium continues to grow and branch, creating a truncated ductal tree comprising immature duct-like cells. The bHLH factor PTF1a, a critical regulator of acinar development, is not expressed and cells producing digestive enzymes are rare. This approach should be generally applicable to study the in vivo functions of other developmental regulators with multiple, temporally distinct roles. 相似文献
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