Xu Sai, Xu Ji-Ping
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, Shandong, People's Republic of China.
Int J Dev Biol. 2019;63(11-12):579-587. doi: 10.1387/ijdb.190242sx.
The aristaless-related homeobox (ARX) gene has become one of most frequently mutated genes which is closely linked with development of the vertebrate central nervous system; however, the molecular and clinical bases of its function in the proliferation and differentiation of the endocrine pancreas have not, to date, been systematically characterized. ARX is considered as a regulator which determines endocrine cell fate and a bio-marker of the pancreatic α-cell. Disruption and mutation of ARX are found to lead to the deletion and reduction of α-cells both in mice models and in humans. Furthermore, expression of ARX is regulated by multiple transcription factors involved in development of the pancreas, such as Ngn3, Isl1, Nkx2.2 and Nkx6.1. Taken together, given the vital importance of glucagon in diabetes treatment, it is possible that ARX may down-regulate exorbitant glucagon levels by reducing the number of α-cells as a direct target; thus, the role of ARX in the maintenance of α-cell identity and quantity should be investigated and summarized. This article mainly focuses on the role of ARX in the endocrine pancreas, introduces the ARX-related animal model and transcription factors, and highlights the latest advances in our understanding in order to provide a clearer theoretical foundation for future scientific research.
无尾相关同源框（ARX）基因已成为与脊椎动物中枢神经系统发育密切相关的最常发生突变的基因之一；然而，迄今为止，其在内分泌胰腺增殖和分化中功能的分子和临床基础尚未得到系统表征。ARX被认为是决定内分泌细胞命运的调节因子和胰腺α细胞的生物标志物。在小鼠模型和人类中均发现ARX的破坏和突变会导致α细胞的缺失和减少。此外，ARX的表达受参与胰腺发育的多种转录因子调控，如Ngn3、Isl1、Nkx2.2和Nkx6.1。综上所述，鉴于胰高血糖素在糖尿病治疗中的至关重要性，ARX有可能作为直接靶点通过减少α细胞数量来下调过高的胰高血糖素水平；因此，应研究和总结ARX在维持α细胞特性和数量方面的作用。本文主要聚焦于ARX在内分泌胰腺中的作用，介绍与ARX相关的动物模型和转录因子，并突出我们最新的认识进展，以便为未来的科学研究提供更清晰的理论基础。
