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用于研究胚胎和成体神经发生的Neurod1-CreER(T2)小鼠品系的构建与鉴定

Generation and characterization of Neurod1-CreER(T2) mouse lines for the study of embryonic and adult neurogenesis.

作者信息

Aprea Julieta, Nonaka-Kinoshita Miki, Calegari Federico

机构信息

DFG-Research Center and Cluster of Excellence for Regenerative Therapies, Dresden, Germany.

出版信息

Genesis. 2014 Oct;52(10):870-8. doi: 10.1002/dvg.22797. Epub 2014 Jun 23.

Abstract

Neurod1 is a transcription factor involved in several developmental programs of the gastrointestinal tract, pancreas, neurosensory, and central nervous system. In the brain, Neurod1 has been shown to be essential for neurogenesis as well as migration, maturation, and survival of newborn neurons during development and adulthood. Interestingly, Neurod1 expression is maintained in a subset of fully mature neurons where its function remains unclear. To study the role of Neurod1, systems are required that allow the temporal and spatial genetic manipulation of Neurod1-expressing cells. To this aim, we have generated four Neurod1-CreER(T2) mouse lines in which CreER(T2) expression, although at different levels, is restricted within areas of physiological Neurod1 expression and Neurod1 positive cells. In particular, the different levels of CreER(T2) expression in different mouse lines offers the opportunity to select the one that is more suited for a given experimental approach. Hence, our Neurod1-CreER(T2) lines provide valuable new tools for the manipulation of newborn neurons during development and adulthood as well as for studying the subpopulation of mature neurons that retain Neurod1 expression throughout life. In this context, we here report that Neurod1 is not only expressed in immature newborn neurons of the adult hippocampus, as already described, but also in fully mature granule cells of the dentate gyrus.

摘要

Neurod1是一种转录因子,参与胃肠道、胰腺、神经感觉和中枢神经系统的多个发育程序。在大脑中,Neurod1已被证明对神经发生以及发育和成年期新生神经元的迁移、成熟和存活至关重要。有趣的是,Neurod1在一部分完全成熟的神经元中持续表达,其功能尚不清楚。为了研究Neurod1的作用,需要能够对表达Neurod1的细胞进行时空基因操作的系统。为此,我们构建了四种Neurod1-CreER(T2)小鼠品系,其中CreER(T2)的表达虽然水平不同,但局限于Neurod1生理表达区域和Neurod1阳性细胞内。特别是,不同小鼠品系中CreER(T2)表达水平的差异为选择更适合特定实验方法的品系提供了机会。因此,我们的Neurod1-CreER(T2)品系为在发育和成年期操纵新生神经元以及研究终生保留Neurod1表达的成熟神经元亚群提供了有价值的新工具。在此背景下,我们在此报告,Neurod1不仅如已描述的那样在成年海马体的未成熟新生神经元中表达,而且在齿状回的完全成熟颗粒细胞中也有表达。

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