Estrogen receptor β expression in the embryonic brain regulates development of calretinin-immunoreactive GABAergic interneurons
Estrogen receptor β expression in the embryonic brain regulates development of calretinin-immunoreactive GABAergic interneurons
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DOI：
10.1073/pnas.0609663103
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发表时间：
2006-12-19
影响因子：
11.1
通讯作者：
Gustafsson, Jan-Ake
中科院分区：
文献类型：
--
作者：
Fan, Xiaotang;Warner, Margaret;Gustafsson, Jan-Ake
我们以前的研究与雌激素受体13敲除（ER ss（-/-））小鼠证明，ER ss是必要的胚胎发育的大脑早在胚胎14.5天（E14.5），并参与神经元迁移。雌激素受体的这种早期效应是出乎意料的，因为雌二醇在脑中的合成和作用发生在E18.5。在本研究中，我们研究了ER SS在发育中的大脑中的分布，并确定了一个人口的ER SS调节的中间神经元。E12.5脑内出现ER ss，主要定位于中脑壁、神经节、下丘脑、丘脑和脑桥基板。在E15.5和E16.5，下丘脑、丘脑和中脑的ER ss表达增加，并出现在边缘前脑。在E18.5，ER β的表达强烈表达在整个大脑，包括小脑和纹状体，而有很少的阳性细胞在脑室区。在丘脑室旁核和束旁核，大多数calretinin免疫阳性的中间神经元表达ER ss。在ER ss（-/-）小鼠中，在E16.5和E18.5时，海马、丘脑和杏仁核中的钙视黄蛋白表达显著低于WT小鼠。在E15.5时，ER ss（-/-）小鼠皮质中的表皮生长因子受体表达低于WT小鼠，并且与WT小鼠不同，在浅表边缘区不存在。这些结果表明，ER β在胚胎脑是必要的钙视黄蛋白免疫反应的GABA能中间神经元的发展和神经元迁移在皮层通过调节表皮生长因子受体的表达在中期和后期胚胎阶段。
Our previous studies with estrogen receptor 13 knockout (ER ss(-/-)) mice demonstrated that ER ss is necessary for embryonic development of the brain as early as embryonic day 14.5 (E14.5) and is involved in neuronal migration. Such early effects of ER were unexpected because estradiol synthesis and action in the brain occur at E18.5. In the present study, we examined the distribution of ER ss in the developing brain and identified a population of ER ss-regulated interneurons. ER ss appears in the brain at E12.5, mainly localized in the wall of the midbrain, neuromere, hypothalamus, thalamus, and basal plate of pons. At E15.5 and E16.5, ER ss expression increased in the hypothalamus, thalamus, and midbrain and appeared in the limbic forebrain. At E18.5, ER ss expression was strongly expressed throughout the brain, including the cerebellum and striatum, whereas there were very few positive cells in the ventricular region. In the paraventricular thalamic nucleus and parafascicular nucleus, most of the calretinin-immunopositive interneurons expressed ER ss. In ER ss(-/-) mice, calretinin expression was markedly lower than in WT mice in the hippocampus, thalamus, and amygdala both at E16.5 and at E18.5. Epidermal growth factor receptor expression was lower in the cortex of ER ss(-/-) than in WT mice at E15.5 and, unlike WT mice, was absent from the superficial marginal zone. These findings suggest that ER ss in the embryonic brain is necessary for the development of calretinin-immunoreactive GABAergic interneurons and for neuronal migration in the cortex through modulating epidermal growth factor receptor expression at middle and later embryonic stages.