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胚胎期、新生期和成年期小鼠大脑中 Pax6 的时空表达模式。

Spatiotemporal expression patterns of Pax6 in the brain of embryonic, newborn, and adult mice.

机构信息

Neuroscience Research Australia, Randwick, Sydney, NSW, 2031, Australia.

出版信息

Brain Struct Funct. 2013 Mar;218(2):353-72. doi: 10.1007/s00429-012-0397-2. Epub 2012 Feb 22.

DOI:10.1007/s00429-012-0397-2
PMID:22354470
Abstract

The transcription factor Pax6 has been reported to specify neural progenitor cell fates during development and maintain neuronal commitments in the adult. The spatiotemporal patterns of Pax6 expression were examined in sagittal and horizontal sections of the embryonic, postnatal, and adult brains using immunohistochemistry and double immunolabeling. The proportion of Pax6-immunopositive cells in various parts of the adult brain was estimated using the isotropic fractionator methodology. It was shown that at embryonic day 11 (E11) Pax6 was robustly expressed in the proliferative neuroepithelia of the ventricular zone in the forebrain and hindbrain, and in the floor and the mesencephalic reticular formation (mRt) in the midbrain. At E12, its expression emerged in the nucleus of the lateral lemniscus in the rhombencephalon and disappeared from the floor of the midbrain. As neurodevelopment proceeds, the expression pattern of Pax6 changes from the mitotic germinal zone in the ventricular zone to become extensively distributed in cell groups in the forebrain and hindbrain, and the expression persisted in the mRt. The majority of Pax6-positive cell groups were maintained until adult life, but the intensity of Pax6 expression became much weaker. Pax6 expression was maintained in the mitotic subventricular zone in the adult brain, but not in the germinal region dentate gyrus in the adult hippocampus. There was no obvious colocalization of Pax6 and NeuN during embryonic development, suggesting Pax6 is found primarily in developing progenitor cells. In the adult brain, however, Pax6 maintains neuronal features of some subtypes of neurons, as indicated by 97.1% of Pax6-positive cells co-expressing NeuN in the cerebellum, 40.7% in the olfactory bulb, 38.3% in the cerebrum, and 73.9% in the remaining brain except the hippocampus. Differentiated tyrosine hydroxylase (TH) neurons were observed in the floor of the E11 midbrain where Pax6 was also expressed, but no obvious colocaliztion of TH and Pax6 was detected. No Pax6 expression was observed in TH-expressing areas in the midbrain at E12, E14, and postnatal day 1. These results support the notion that Pax6 plays pivotal roles in specifying neural progenitor cell commitments and maintaining certain mature neuronal fates.

摘要

转录因子 Pax6 已被报道在发育过程中指定神经祖细胞命运,并在成年期维持神经元的命运。使用免疫组织化学和双重免疫标记法,在胚胎、出生后和成年期大脑的矢状和水平切片中检查 Pax6 表达的时空模式。使用各向同性分数器方法估计成年大脑各部分中 Pax6 免疫阳性细胞的比例。结果表明,在胚胎第 11 天(E11),Pax6 在大脑前脑和后脑的室管膜区的增殖性神经上皮中以及中脑的地板和中脑网状结构(mRt)中强烈表达。在 E12,它的表达出现在后脑的外侧丘系核中,并从中脑地板消失。随着神经发育的进行,Pax6 的表达模式从室管膜区的有丝分裂生发区变为广泛分布于大脑前脑和后脑的细胞群,并且表达持续存在于 mRt 中。大多数 Pax6 阳性细胞群维持到成年期,但 Pax6 表达的强度变得弱得多。Pax6 表达在成年大脑的有丝分裂室下区维持,但在成年海马齿状回的生殖区中没有。在胚胎发育过程中,Pax6 和 NeuN 没有明显的共定位,表明 Pax6 主要存在于发育中的祖细胞中。然而,在成年大脑中,Pax6 维持一些神经元亚型的神经元特征,如小脑中 97.1%的 Pax6 阳性细胞共表达 NeuN,嗅球中 40.7%,大脑中 38.3%,除海马外的其余大脑中为 73.9%。在 Pax6 表达的中脑地板上观察到分化的酪氨酸羟化酶(TH)神经元,但没有检测到 TH 和 Pax6 的明显共定位。在 E11 中脑、E12、E14 和出生后第 1 天的 TH 表达区域未观察到 Pax6 表达。这些结果支持 Pax6 在指定神经祖细胞命运和维持某些成熟神经元命运方面发挥关键作用的观点。

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