Satb1 is an activity-modulated transcription factor required for the terminal differentiation and connectivity of medial ganglionic eminence-derived cortical interneurons.
Satb1 is an activity-modulated transcription factor required for the terminal differentiation and connectivity of medial ganglionic eminence-derived cortical interneurons.
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DOI：
10.1523/jneurosci.3583-12.2012
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发表时间：
2012-12-05
期刊：
影响因子：
--
通讯作者：
Fishell G
中科院分区：
文献类型：
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作者：
Close J;Xu H;De Marco García N;Batista-Brito R;Rossignol E;Rudy B;Fishell G
尽管以前的工作发现了对表达小白蛋白(PV)和生长抑素(SST)的中间神经元的指定和迁移至关重要的转录因子，但这些细胞类型的末端分化、连通性和生存所需的内在因子仍未确定。在这里，我们证明，在皮质中间神经元亚群中，特殊的富含AT结合蛋白(Satb1)在这一能力中发挥作用。我们发现，有条件地去除小鼠中间神经元中的Satb1会导致出生后第21天所有皮质层中大部分表达SST的细胞以及第四层和第六层中一些表达PV的细胞丢失。在Satb1突变小鼠中，表达SST的细胞最初迁移到大脑皮层，但接受的传入输入水平降低，并在出生后第一周开始死亡。电生理特征表明，中间神经元Satb1功能的丧失导致兴奋性主细胞功能抑制的丧失。这些数据表明，Satb1是MGE来源的神经元间分化、连接和存活所必需的。
Although previous work identified transcription factors crucial for the specification and migration of parvalbumin (PV) and somatostatin (SST)-expressing interneurons, the intrinsic factors required for the terminal differentiation, connectivity and survival of these cell types remain uncharacterized. Here we demonstrate that, within subpopulations of cortical interneurons, the special AT-rich binding protein (Satb1) functions in this capacity. We find that conditional removal of Satb1 in mouse interneurons results in the loss of a majority of SST-expressing cells across all cortical layers, as well as some PV-expressing cells in layers IV and VI, by postnatal day 21. SST-expressing cells initially migrate to the cortex in Satb1 mutant mice, but receive reduced levels of afferent input and begin to die during the first postnatal week. Electrophysiological characterization indicates that loss of Satb1 function in interneurons results in a loss of functional inhibition of excitatory principal cells. These data suggest that Satb1 is required for MGE-derived interneuron differentiation, connectivity and survival.