Genetic Labeling Reveals Novel Cellular Targets of Schizophrenia Susceptibility Gene: Distribution of GABA and Non-GABA ErbB4-Positive Cells in Adult Mouse Brain
Genetic Labeling Reveals Novel Cellular Targets of Schizophrenia Susceptibility Gene: Distribution of GABA and Non-GABA ErbB4-Positive Cells in Adult Mouse Brain
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DOI：
10.1523/jneurosci.2021-14.2014
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发表时间：
2014-10-01
影响因子：
5.3
通讯作者：
Mei, Lin
中科院分区：
文献类型：
--
作者：
Bean, Jonathan C.;Lin, Thiri W.;Mei, Lin
神经调节蛋白1（NRG 1）及其受体ErbB 4是精神分裂症的危险基因。NRG 1-ErbB 4信号在神经发育中起着关键作用，并调节神经传递和突触可塑性。然而，其细胞靶点仍存在争议。ErbB 4被认为在兴奋性神经元中表达，尽管最近的研究对这一观点提出了质疑。使用在ErbB 4基因启动子下表达荧光蛋白的小鼠，我们确定ErbB 4在哪些细胞中表达及其身份。ErbB 4在小鼠大脑中广泛表达，在杏仁核和皮质中表达最高。在新生和成年小鼠的皮质、海马、基底神经节和大部分杏仁核中，几乎所有ErbB 4阳性细胞都是GABA能的，这表明GABA能传递是这些区域中NRG 1-ErbB 4信号传导的主要靶点。非GABA能，ErbB 4阳性细胞存在于丘脑，下丘脑，中脑和后脑。特别是，ErbB 4在中缝核的肾上腺素能神经元中表达，但在蓝斑的去甲肾上腺素能神经元中不表达。在下丘脑中，ErbB 4存在于表达催产素的神经元中。最后，ErbB 4在皮质下区域的一组细胞中表达，这些细胞对S100钙结合蛋白β呈阳性。这些结果鉴定了NRG 1-ErbB 4信号传导的新细胞靶点。
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 beta. These results identify novel cellular targets of NRG1-ErbB4 signaling.