Differentiation of the dopaminergic phenotype in the olfactory system of neonatal and adult mice
Differentiation of the dopaminergic phenotype in the olfactory system of neonatal and adult mice
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DOI：
10.1002/cne.20320
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发表时间：
2004-11-22
影响因子：
2.5
通讯作者：
Baker, H
中科院分区：
文献类型：
--
作者：
Saino-Saito, S;Sasaki, H;Baker, H
嗅球(OB)中间神经元主要来源于出生后前脑室下区(SVZa)的前体细胞，并在吻侧迁移流(RMS)中迁移到OB。祖细胞分化为表型多样的颗粒细胞和小球周围细胞的机制尚不明确。为了可视化球周多巴胺(DA)神经元分化的时空特征，用9kb酪氨酸羟化酶(TH)启动子驱动LacZ或增强型绿色荧光蛋白(EGFP)报告基因，对两个独立获得的转基因小鼠品系进行了分析。两位记者都显示出相似的新生儿表达，从RMS的低水平，到浅颗粒细胞层的中等水平，到球周区相对较大的细胞(可能是外部丛生细胞)的强表达。在RMS中未检测到TH基因的表达，但与外源基因共定位于新生儿浅层颗粒和小球周围细胞。相比之下，成人的TH蛋白进一步局限于肾小球周围细胞。为了证明EGFP和TH的转录调控是相同的，在成人单侧鼻孔闭合所产生的气味剥夺的同侧OB中，表达被显示出类似的下降。在先前假设调节OB DA表达的两个基因中，只有孤儿受体Nurr1的调节表达，而不是含有同源盒的基因DLX-1和DLX-2的表达，与调节DA表型的作用一致。这些数据首次证明，新生儿DA表型分化始于RMS内迁移前体细胞的低水平转录，最终在嗅觉受体细胞支配的球周细胞中表达活性依赖的蛋白。J.Comp.神经。479：389-398,2004。(C)2004年Wiley-Liss公司
Olfactory bulb (OB) interneurons are derived primarily postnatally from progenitors in the anterior subventricular zone (SVZa) and migrate to the OB in the rostral migratory stream (RMS). Progenitors differentiate into phenotypically diverse granule and periglomerular cells by as yet undefined mechanisms. To visualize spatiotemporal aspects of periglomerular dopamine (DA) neuron differentiation, two independently derived transgenic mouse lines were analyzed with a 9-kb tyrosine hydroxylase (TH) promoter to drive either a LacZ or an enhanced green fluorescent protein (EGFP) reporter gene. Both reporters showed similar neonatal expression that varied from low levels in RMS, to moderate in the superficial granule cell layer, to strong in relatively large cells, possibly external tufted cells, in the periglomerular region. TH mRNA and protein were not detected in the RMS but were colocalized with the transgenes in neonatal superficial granule and periglomerular cells. By comparison, TH protein in adults was further limited to periglomerular cells. To demonstrate that transcriptional regulation was the same for EGFP and TH, expression was shown to decline similarly in the OB ipsilateral to odor deprivation produced by adult unilateral naris closure. Of two genes previously hypothesized to regulate OB DA expression, only regulated expression of the orphan receptor Nurr1, but not the homeobox-containing genes Dlx-1 and -2, was consistent with a role in regulation of the DA phenotype. These data demonstrate for the first time that DA phenotypic differentiation in neonates begins with low-level transcription in migrating progenitors in the RMS and culminates with activity-dependent protein expression in periglomerular cells innervated by olfactory receptor cells. J. Comp. Neurol. 479:389-398, 2004. (C) 2004 Wiley-Liss, Inc.