Fate of transient catecholaminergic cell types revealed by site-specific recombination in transgenic mice

Fate of transient catecholaminergic cell types revealed by site-specific recombination in transgenic mice
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DOI:
10.1002/jnr.20229
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发表时间:
2004-10-01
影响因子:
4.2
通讯作者:
Kobayashi, K
Kobayashi, K
中科院分区:
医学3区
文献类型:
--
作者:
Matsushita, N;Kobayashi, K;Kobayashi, K

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在脊椎动物发育过程中,产生儿茶酚胺的细胞类型由特定的神经元谱系产生。在胚胎发育期间,儿茶酚胺能表型也在非儿茶酚胺能组织的某些细胞类型中瞬时表达,包括感觉神经节、肠神经节和神经管的腹侧部分。然而,在以后的发展阶段的短暂的儿茶酚胺能细胞类型的命运,尚未阐明。我们开发了一个Cre-/OXP-介导的重组系统的多巴胺β-羟化酶(DBH)启动子的控制下,驱动典型的去甲肾上腺素能和肾上腺素能细胞群,以及在短暂的儿茶酚胺能细胞类型的基因表达。Cre重组酶在转基因小鼠中的表达导致在成年阶段去甲肾上腺素能和肾上腺素能细胞群中的有效重组。在颅神经/脊髓运动神经元和感觉/肠神经节神经元中也诱导重组。在转基因小鼠胚胎中的重组模式的分析表明,在产前发育过程中,在这两种细胞类型表现出典型的和短暂的儿茶酚胺能表型的重组的发生。由于DBH基因启动子在胚胎发育过程中在腹侧神经管和感觉神经节中瞬时表达,我们的研究结果提供了证据表明,在这些组织中表现出瞬时儿茶酚胺能表型的细胞类型注定要在随后的分化过程中成为成熟的运动神经元或感觉神经节神经元。(C)2004 Wiley-Liss,Inc.
Catecholamine-producing cell types are generated from specified neuronal lineages during vertebrate development. The catecholaminergic phenotype is also expressed transiently in some cell types in non-catecholaminergic tissues, including the sensory ganglia, enteric ganglia, and ventral portions of the neural tube during embryonic development. The fate of the transient catecholaminergic cell types at later developmental stages, however, has not been elucidated. We developed a Cre-/OXP-mediated recombination system under the control of the dopamine beta-hydroxylase (DBH) promoter, which drives gene expression in typical noradrenergic and adrenergic cell groups as well as in transient catecholaminergic cell types. Expression of Cre recombinase in transgenic mice resulted in an efficient recombination in noradrenergic and adrenergic cell groups at the adult stage. The recombination was also induced in the cranial nerve/spinal cord motor neurons and sensory/enteric ganglion neurons. Analysis of recombination patterns in transgenic mouse embryos showed the occurrence of recombination during prenatal development in both cell types exhibiting the typical and transient catecholaminergic phenotypes. Because the DBH gene promoter is expressed transiently in the ventral neural tube and sensory ganglion during embryonic development, our results provide evidence that the cell types showing a transient catecholaminergic phenotype in these tissues are destined to become mature motor neurons or sensory ganglion neurons during subsequent differentiation. (C) 2004 Wiley-Liss, Inc.