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Cholinergic differentiation occurs early in mouse sympathetic neurons and requires Phox2b.

机译:胆碱能分化发生在小鼠交感神经元的早期,需要Phox2b。

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The generation of neurotransmitter identity in the autonomic nervous system is a classical model system to study the development of neuronal diversity. Analysis of the expression of genes coding for enzymes of noradrenaline biosynthesis in the sympathoadrenal system allowed the characterization of factors involved in the differentiation of the noradrenergic transmitter phenotype. The development of cholinergic properties in the autonomic system is less well understood. Here we show that expression of mRNAs for choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT), both encoded by the cholinergic gene locus, is induced in mouse sympathetic ganglia at embryonic day 11 (E11). Positive cells amount to more than 50% of Phox2b-positive sympathetic cells at cervical levels. The proportion declines caudally, decreasing to approximately 20% of Phox2b-positive cells at lower thoracic levels. In the adrenal anlage, ChAT and VAChT mRNA are largely undetectable at E11 and E13. In micehomozygous for a mutational inactivation of the transcription factor Phox2b, ChAT and VAChT mRNA expression is absent from sympathetic ganglia. The data show that expression from the cholinergic gene locus is regulated differently in sympathetic neurons and adrenal chromaffin cells. Phox2b is required for development of cholinergic neurons but does not suffice to support cholinergic properties in chromaffin cells.
机译:自主神经系统中神经递质同一性的产生是研究神经元多样性发展的经典模型系统。分析交感肾上腺系统中去甲肾上腺素生物合成酶编码基因的表达,可以表征参与去甲肾上腺素能递质表型分化的因素。自主系统中胆碱能特性的发展还不太清楚。在这里,我们显示了胆碱能基因位点编码的胆碱乙酰转移酶(ChAT)和囊泡乙酰胆碱转运蛋白(VAChT)的mRNA表达在小鼠交感神经节胚胎第11天(E11)诱导。在宫颈水平上,阳性细胞占Phox2b阳性交感细胞的50%以上。该比例尾部下降,在较低的胸腔水平下减少到大约20%的Phox2b阳性细胞。在肾上腺疾病中,ChAT和VAChT mRNA在E11和E13处基本检测不到。在转录因子Phox2b突变灭活的小鼠纯合子中,交感神经节中不存在ChAT和VAChT mRNA表达。数据显示,在交感神经元和肾上腺嗜铬细胞中,胆碱能基因基因座的表达受到不同的调节。 Phox2b是胆碱能神经元发育所必需的,但不足以支持嗜铬细胞中的胆碱能特性。

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