基因标记揭示了神经调节蛋白1在小鼠大脑中的空间和细胞表达模式。

Genetic labeling reveals spatial and cellular expression pattern of neuregulin 1 in mouse brain.

作者信息

Ding Chen-Yun, Ding Yan-Ting, Ji Haifeng, Wang Yao-Yi, Zhang Xinwen, Yin Dong-Min

机构信息

Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China.

Center of Implant Dentistry, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, 110002, China.

出版信息

Cell Biosci. 2023 May 5;13(1):79. doi: 10.1186/s13578-023-01032-4.

DOI:10.1186/s13578-023-01032-4

PMID:37147705

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10161477/

Abstract

BACKGROUND

Where the gene is expressed determines the function of the gene. Neuregulin 1 (Nrg1) encodes a tropic factor and is genetically linked with several neuropsychiatry diseases such as schizophrenia, bipolar disorder and depression. Nrg1 has broad functions ranging from regulating neurodevelopment to neurotransmission in the nervous system. However, the expression pattern of Nrg1 at the cellular and circuit levels in rodent brain is not full addressed.

METHODS

Here we used CRISPR/Cas9 techniques to generate a knockin mouse line (Nrg1) that expresses a P2A-Cre cassette right before the stop codon of Nrg1 gene. Since Cre recombinase and Nrg1 are expressed in the same types of cells in Nrg1 mice, the Nrg1 expression pattern can be revealed through the Cre-reporting mice or adeno-associated virus (AAV) that express fluorescent proteins in a Cre-dependent way. Using unbiased stereology and fluorescence imaging, the cellular expression pattern of Nrg1 and axon projections of Nrg1-positive neurons were investigated.

RESULTS

In the olfactory bulb (OB), Nrg1 is expressed in GABAergic interneurons including periglomerular (PG) and granule cells. In the cerebral cortex, Nrg1 is mainly expressed in the pyramidal neurons of superficial layers that mediate intercortical communications. In the striatum, Nrg1 is highly expressed in the Drd1-positive medium spiny neurons (MSNs) in the shell of nucleus accumbens (NAc) that project to substantia nigra pars reticulata (SNr). In the hippocampus, Nrg1 is mainly expressed in granule neurons in the dentate gyrus and pyramidal neurons in the subiculum. The Nrg1-expressing neurons in the subiculum project to retrosplenial granular cortex (RSG) and mammillary nucleus (MM). Nrg1 is highly expressed in the median eminence (ME) of hypothalamus and Purkinje cells in the cerebellum.

CONCLUSIONS

Nrg1 is broadly expressed in mouse brain, mainly in neurons, but has unique expression patterns in different brain regions.

摘要

背景

基因的表达位置决定了基因的功能。神经调节蛋白1（Nrg1）编码一种营养因子，并且在遗传上与多种神经精神疾病相关，如精神分裂症、双相情感障碍和抑郁症。Nrg1具有广泛的功能，从调节神经发育到神经系统中的神经传递。然而，Nrg1在啮齿动物大脑细胞和神经回路水平上的表达模式尚未得到充分研究。

方法

在此，我们使用CRISPR/Cas9技术构建了一个敲入小鼠品系（Nrg1），该品系在Nrg1基因的终止密码子之前表达一个P2A-Cre盒。由于Cre重组酶和Nrg1在Nrg1小鼠的相同类型细胞中表达，因此可以通过在Cre依赖性方式下表达荧光蛋白的Cre报告小鼠或腺相关病毒（AAV）来揭示Nrg1的表达模式。使用无偏倚的立体学和荧光成像技术，研究了Nrg1的细胞表达模式以及Nrg1阳性神经元的轴突投射。

结果

在嗅球（OB）中，Nrg1在包括球周（PG）和颗粒细胞在内的GABA能中间神经元中表达。在大脑皮层中，Nrg1主要在介导皮层间通讯的浅层锥体神经元中表达。在纹状体中，Nrg1在伏隔核（NAc）壳中的Drd1阳性中型多棘神经元（MSN）中高度表达，这些神经元投射到黑质网状部（SNr）。在海马体中，Nrg1主要在齿状回的颗粒神经元和下托的锥体神经元中表达。下托中表达Nrg1的神经元投射到 retrosplenial颗粒皮层（RSG）和乳头体核（MM）。Nrg1在下丘脑的正中隆起（ME）和小脑中的浦肯野细胞中高度表达。