The Spatiotemporal Pattern of Glis3 Expression Indicates a Regulatory Function in Bipotent and Endocrine Progenitors during Early Pancreatic Development and in Beta, PP and Ductal Cells.
The Spatiotemporal Pattern of Glis3 Expression Indicates a Regulatory Function in Bipotent and Endocrine Progenitors during Early Pancreatic Development and in Beta, PP and Ductal Cells.
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DOI：
10.1371/journal.pone.0157138
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Jetten AM
中科院分区：
文献类型：
--
作者：
Kang HS;Takeda Y;Jeon K;Jetten AM
转录因子Glis类似物3(GLIS3)与新生儿、1型和2型糖尿病的发生有关。在这项研究中，我们检测了GLIS3蛋白在胚胎和新生胰腺发育过程中的时空表达及其在PP细胞中的功能。为了更深入地了解GLIS3在胰腺发育中的功能，我们检测了GLIS3蛋白在表达GLIS3-EGFP融合蛋白的敲打小鼠品系中的时空表达。免疫组织化学结果显示，GLIS3-EGFP在胰腺发育早期(E11.5和E12.5)未见表达，在E13.5和15.5未见表达，提示GLIS3在多能胰腺祖细胞中不表达。GLIS3首先在E13.5位在主干结构域的双能前体细胞核中被检测到，它与Sox9、Hnf6和Pdx1共定位。它在胰岛β细胞、胰岛β细胞、胰岛PP细胞以及导管细胞的胞核中均有表达。GLIS3缺乏症显著减少，而外源GLIS3诱导Ppy表达，正如胰岛素所报道的那样。总之，我们的研究表明，GLIS3蛋白在胚胎和新生儿胰腺发育过程中表现出时间和细胞类型特异性的表达模式，这与GLIS3在促进内分泌祖细胞生成、调节胰岛素和Ppy在β细胞和PP细胞中的表达以及导管形态形成方面的调节作用是一致的。
The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and type 2 diabetes. In this study, we examined the spatiotemporal expression of Glis3 protein during embryonic and neonatal pancreas development as well as its function in PP cells. To obtain greater insights into the functions of Glis3 in pancreas development, we examined the spatiotemporal expression of Glis3 protein in a knockin mouse strain expressing a Glis3-EGFP fusion protein. Immunohistochemistry showed that Glis3-EGFP was not detectable during early pancreatic development (E11.5 and E12.5) and at E13.5 and 15.5 was not expressed in Ptf1a+ cells in the tip domains indicating that Glis3 is not expressed in multipotent pancreatic progenitors. Glis3 was first detectable at E13.5 in the nucleus of bipotent progenitors in the trunk domains, where it co-localized with Sox9, Hnf6, and Pdx1. It remained expressed in preductal and Ngn3+ endocrine progenitors and at later stages becomes restricted to the nucleus of pancreatic beta and PP cells as well as ductal cells. Glis3-deficiency greatly reduced, whereas exogenous Glis3, induced Ppy expression, as reported for insulin. Collectively, our study demonstrates that Glis3 protein exhibits a temporal and cell type-specific pattern of expression during embryonic and neonatal pancreas development that is consistent with a regulatory role for Glis3 in promoting endocrine progenitor generation, regulating insulin and Ppy expression in beta and PP cells, respectively, and duct morphogenesis.