Maturation-promoting activity of SATB1 in MGE-derived cortical interneurons.
Maturation-promoting activity of SATB1 in MGE-derived cortical interneurons.
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DOI：
10.1016/j.celrep.2012.10.003
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发表时间：
2012-11-29
期刊：
影响因子：
8.8
通讯作者：
Pachnis V
中科院分区：
文献类型：
--
作者：
Denaxa M;Kalaitzidou M;Garefalaki A;Achimastou A;Lasrado R;Maes T;Pachnis V
皮质中间神经元亚型的产生是由遗传程序控制的，这些遗传程序在腹侧前脑中被激活，并在长时间的抑制性神经元发育期间展开。LIM-homeodomain蛋白LHX 6是关键的所有皮层中间神经元起源于内侧神经节隆起的发展，但LHX 6下游的分子机制，控制终末分化的生长抑素和小白蛋白表达的中间神经元在皮质内仍然未知。在这里，我们提供的证据表明，核基质和基因组组织者蛋白SATB 1诱导的神经元的活动和功能下游的Lhx 6控制过渡的切向迁移未成熟的中间神经元的终末分化生长抑素（SST）表达亚型。我们的实验提供了一个分子框架，以了解遗传和表观遗传机制，指定但不成熟的皮层中间神经元获得亚型定义的分子和形态生理学特征，使他们能够整合和功能内皮层电路。Satb 1在MGE衍生的皮质中间神经元中特异性表达Satb 1是MGE衍生的皮质中间神经元在体内成熟所必需的Satb 1促进Lhx 6下游SST+皮质中间神经元的成熟神经元活性诱导Satb 1在未成熟皮质中间神经元中的表达皮质中间神经元在脑回路的功能中起关键作用，并且中间神经元的异常发育导致严重的神经发育障碍。Pachnis及其同事证明，基因组组织者SATB 1可以被神经元活动激活，并在转录因子LHX 6的下游发挥作用，以促进表达生长抑素的中间神经元的分化。缺乏SATB 1的小鼠不能分化这一关键的中间神经元组。这些发现确定了哺乳动物皮层神经回路形成的关键调节因子。
The generation of cortical interneuron subtypes is controlled by genetic programs that are activated in the ventral forebrain and unfold during the prolonged period of inhibitory neuron development. The LIM-homeodomain protein LHX6 is critical for the development of all cortical interneurons originating in the medial ganglionic eminence, but the molecular mechanisms that operate downstream of LHX6 to control the terminal differentiation of somatostatin- and parvalbumin-expressing interneurons within the cortex remain unknown. Here, we provide evidence that the nuclear matrix and genome organizer protein SATB1 is induced by neuronal activity and functions downstream of Lhx6 to control the transition of tangentially migrating immature interneurons into the terminally differentiated Somatostatin (SST)-expressing subtype. Our experiments provide a molecular framework for understanding the genetic and epigenetic mechanisms by which specified but immature cortical interneurons acquire the subtype-defining molecular and morphophysiological characteristics that allow them to integrate and function within cortical circuits. ► Satb1 is specifically expressed in MGE-derived cortical interneurons ► Satb1 is required for the maturation of MGE-derived cortical interneurons in vivo ► Satb1 promotes the maturation of SST+ cortical interneurons downstream of Lhx6 ► Neuronal activity induces expression of Satb1 in immature cortical interneurons Cortical interneurons play a crucial role in the function of cerebral circuits, and abnormal development of interneurons results in severe neurodevelopmental disorders. Pachnis and colleagues demonstrate that the genome organizer SATB1 can be activated by neuronal activity and functions downstream of the transcription factor LHX6 to promote the differentiation of somatostatin-expressing interneurons. Mice deficient in SATB1 fail to differentiate this critical group of interneurons. These findings identify a key regulator of neural circuit formation in the mammalian cortex.
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影响因子：
3.5
作者：
Neddens, Joerg;Buonanno, Andres
通讯作者：
Buonanno, Andres
影响因子：
5.3
作者：
Miyoshi, Goichi;Butt, Simon J. B.;Fishell, Gord
通讯作者：
Fishell, Gord
DOI：
10.1093/cercor/bhs159
发表时间：
2013-08
期刊：
Cerebral cortex (New York, N.Y. : 1991)
影响因子：
--
作者：
Neves G;Shah MM;Liodis P;Achimastou A;Denaxa M;Roalfe G;Sesay A;Walker MC;Pachnis V
通讯作者：
Pachnis V
影响因子：
16.2
作者：
Taniguchi H;He M;Wu P;Kim S;Paik R;Sugino K;Kvitsiani D;Fu Y;Lu J;Lin Y;Miyoshi G;Shima Y;Fishell G;Nelson SB;Huang ZJ
通讯作者：
Huang ZJ
影响因子：
16.2
作者：
Xu, Qing;Guo, Lihua;Moore, Holly;Waclaw, Ronald R.;Campbell, Kenneth;Anderson, Stewart A.
通讯作者：
Anderson, Stewart A.