Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas.
Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas.
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作者：
Du A;Hunter CS;Murray J;Noble D;Cai CL;Evans SM;Stein R;May CL
胰腺发育过程中成熟细胞类型的产生取决于许多调节和信号蛋白的表达。在这项研究中，我们测试的假设，即转录调节因子胰岛-1（Isl-1），其表达首先在发育中的胰腺的间充质和上皮细胞中检测到，后来仅限于成熟的胰岛细胞，参与胰岛细胞的终末分化和胰岛质量的维持。为了研究Isl-1在胰腺上皮细胞次级转化过程中的作用，使用Cre/LoxP技术从胚胎第13.5天开始有条件地特异性删除Isl-1。缺乏Isl-1的内分泌前体细胞不能成熟为功能性胰岛细胞。出生后内分泌细胞群的扩张受损，因此Isl-1缺陷小鼠糖尿病。此外，MafA是胰岛素基因和β细胞功能的有效调节剂，被鉴定为Isl-1的直接转录靶标。这些结果证明了Isl-1在第二波产生胰岛细胞的成熟、增殖和存活中的需要。
The generation of mature cell types during pancreatic development depends on the expression of many regulatory and signaling proteins. In this study, we tested the hypothesis that the transcriptional regulator Islet-1 (Isl-1), whose expression is first detected in the mesenchyme and epithelium of the developing pancreas and is later restricted to mature islet cells, is involved in the terminal differentiation of islet cells and maintenance of islet mass. To investigate the role of Isl-1 in the pancreatic epithelium during the secondary transition, Isl-1 was conditionally and specifically deleted from embryonic day 13.5 onward using Cre/LoxP technology. Isl-1–deficient endocrine precursors failed to mature into functional islet cells. The postnatal expansion of endocrine cell mass was impaired, and consequently Isl-1 deficient mice were diabetic. In addition, MafA, a potent regulator of the Insulin gene and β-cell function, was identified as a direct transcriptional target of Isl-1. These results demonstrate the requirement for Isl-1 in the maturation, proliferation, and survival of the second wave of hormone-producing islet cells.