The homeodomain protein PDX1 is required at mid-pancreatic development for the formation of the exocrine pancreas
The homeodomain protein PDX1 is required at mid-pancreatic development for the formation of the exocrine pancreas
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DOI：
10.1016/j.ydbio.2005.07.026
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发表时间：
2005-10-01
影响因子：
2.7
通讯作者：
MacDonald, RJ
中科院分区：
文献类型：
--
作者：
Hale, MA;Kagami, H;MacDonald, RJ
同源异型蛋白PDX 1在整个胰腺发育过程中表达，并被认为在多个阶段发挥重要作用。我们描述了一个tet关闭的监管计划，以管理在子宫内的Pdx 1的表达的属性。Pdx 1表达的停止在越来越晚的妊娠时间阻止胰腺的发展，在进步和形态学不同的阶段，并提供了机会，以评估Pdx 1在每个阶段的需求。胚胎PDX 1在开始多西环素治疗妊娠小鼠的1天内被消耗到低于有效水平。我们表明，PDX 1，这是必要的胰腺发育早期，也需要后来的腺泡组织，胰腺的隔间，产生消化酶的发生。没有PDX 1，腺泡不会形成;前体上皮继续生长并分支，产生包含未成熟导管样细胞的截短导管树。bHLH因子PTF 1a是腺泡发育的关键调节因子，不表达，产生消化酶的细胞很少。这种方法应该是普遍适用于研究在体内功能的其他发育调节多种，时间上不同的角色。(c)2005年爱思唯尔公司All rights reserved.
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 I 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. (c) 2005 Elsevier Inc. All rights reserved.