Distinct cis-regulatory elements from the Dlx1/Dlx2 locus mark different progenitor cell populations in the ganglionic eminences and different subtypes of adult cortical interneurons

Distinct cis-regulatory elements from the Dlx1/Dlx2 locus mark different progenitor cell populations in the ganglionic eminences and different subtypes of adult cortical interneurons
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DOI:
10.1523/jneurosci.4725-06.2007
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发表时间:
2007-05-09
影响因子:
5.3
通讯作者:
Ekker, Marc
Ekker, Marc
中科院分区:
医学1区
文献类型:
--
作者:
Ghanem, Noel;Yu, Man;Ekker, Marc

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皮质GABA能中间神经元的不同亚型提供神经网络功能不可或缺的抑制信号。Dlx同源框基因在调节其发育和功能中具有核心作用。我们的特点是三个顺式调控序列参与前脑表达脊椎动物Dlx基因:上游调控元件2(URE 2),I12 b,和I56 i的活动。这三个调节元件显示区域和时间的差异,他们的活动在外侧神经节隆起(LGE),内侧神经节隆起(MGE),和尾神经节隆起(CGE)和标签不同的人口切线迁移神经元在胚胎第12.5天(E12.5)和E13.5。我们提供的证据表明,背内侧和腹侧MGE是不同的来源切线迁移神经元在妊娠中期。在成人皮质中,URE 2和I12 b/I56 i在小白蛋白、钙网膜蛋白、神经肽Y和神经元型一氧化氮合酶阳性中间神经元中差异表达; I12 b和I56 i在生长抑素、血管活性肠肽和钙结合蛋白阳性中间神经元中特异性活跃。这些数据表明,中间神经元亚型使用Dlx 1/Dlx 2增强子的不同组合,从它们被指定到成年的时间。
Distinct subtypes of cortical GABAergic interneurons provide inhibitory signals that are indispensable for neural network function. The Dlx homeobox genes have a central role in regulating their development and function. We have characterized the activity of three cis-regulatory sequences involved in forebrain expression of vertebrate Dlx genes: upstream regulatory element 2 (URE2), I12b, and I56i. The three regulatory elements display regional and temporal differences in their activities within the lateral ganglionic eminence (LGE), medial ganglionic eminence (MGE), and caudal ganglionic eminence (CGE) and label distinct populations of tangentially migrating neurons at embryonic day 12.5 (E12.5) and E13.5. We provide evidence that the dorsomedial and ventral MGE are distinct sources of tangentially migrating neurons during midgestation. In the adult cortex, URE2 and I12b/I56i are differentially expressed in parvalbumin-, calretinin-, neuropeptide Y-, and neuronal nitric oxide synthase-positive interneurons; I12b and I56i were specifically active in somatostatin-, vasoactive intestinal peptide-,and calbindin-positive interneurons. These data suggest that interneuron subtypes use distinct combinations of Dlx1/Dlx2 enhancers from the time they are specified through adulthood.