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

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

doi:10.1186/s13578-023-01032-4

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

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

Authors

Chen-Yun Ding^#^{1

2}, Yan-Ting Ding^#¹, Haifeng Ji^{1

3}, Yao-Yi Wang¹, Xinwen Zhang^{4

5}, Dong-Min Yin^{6

7}

Affiliations

¹ Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China.
² Center of Implant Dentistry, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, 110002, China.
³ Shanghai Changning Mental Health Center, Affiliated to East China Normal University, Shanghai, 200335, China.
⁴ Center of Implant Dentistry, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, 110002, China. zhangxinwen@cmu.edu.cn.
⁵ Laboratory Animal Centre, China Medical University, Shenyang, 110001, China. zhangxinwen@cmu.edu.cn.
⁶ Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Science, East China Normal University, Shanghai, 200062, China. dmyin@brain.ecnu.edu.cn.
⁷ NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai, Shanghai, 200062, China. dmyin@brain.ecnu.edu.cn.

^# Contributed equally.

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^Cre/+) 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^Cre/+ 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.

Keywords: Cerebral cortex; Cre-reporting mice; Hippocampus; Hypothalamus, cerebellum, axon projection; Neuregulin 1; Olfactory bulb; Striatum.

Grants and funding

2021ZD020250/Key Technologies Research and Development Program