title: Genetic labeling reveals novel cellular targets of schizophrenia susceptibility gene: distribution of GABA and non-GABA ErbB4-positive cells in adult mouse brain.
abstract: Neuregulin 1 (NRG1) and its receptor ErbB4 are schizophrenia risk genes. NRG1-ErbB4 signaling plays a critical role in neural development and regulates neurotransmission and synaptic plasticity. Nevertheless, its cellular targets remain controversial. ErbB4 was thought to express in excitatory neurons, although recent studies disputed this view. Using mice that express a fluorescent protein under the promoter of the ErbB4 gene, we determined in what cells ErbB4 is expressed and their identity. ErbB4 was widely expressed in the mouse brain, being highest in amygdala and cortex. Almost all ErbB4-positive cells were GABAergic in cortex, hippocampus, basal ganglia, and most of amygdala in neonatal and adult mice, suggesting GABAergic transmission as a major target of NRG1-ErbB4 signaling in these regions. Non-GABAergic, ErbB4-positive cells were present in thalamus, hypothalamus, midbrain, and hindbrain. In particular, ErbB4 is expressed in serotoninergic neurons of raphe nuclei but not in norepinephrinergic neurons of the locus ceruleus. In hypothalamus, ErbB4 is present in neurons that express oxytocin. Finally, ErbB4 is expressed in a group of cells in the subcortical areas that are positive for S100 calcium binding protein β. These results identify novel cellular targets of NRG1-ErbB4 signaling.
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Bean
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: Thiri W
authors.initials: TW
authors.lastname: Lin
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: Anupama
authors.identifier: http://orcid.org/0000-0001-9731-3043
authors.initials: A
authors.lastname: Sathyamurthy
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, China.
authors.forename: Dong-Min
authors.initials: DM
authors.lastname: Yin
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, Charlie Norwood Veterans Administration Medical Center, Augusta, Georgia 30904, and.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912, Charlie Norwood Veterans Administration Medical Center, Augusta, Georgia 30904, and lmei@gru.edu.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D002478:Cells, Cultured; D005968:Glutamate Decarboxylase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D066247:Receptor, ErbB-4 / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: ErbB4; NRG1; Neuregulin; S100β; oxytocin; serotonin