Satb1 Ablation Alters Temporal Expression of Immediate Early Genes and Reduces Dendritic Spine Density during Postnatal Brain Development
Satb1 Ablation Alters Temporal Expression of Immediate Early Genes and Reduces Dendritic Spine Density during Postnatal Brain Development
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DOI：
10.1128/mcb.05917-11
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发表时间：
2012-01-01
影响因子：
5.3
通讯作者：
Kohwi, Yoshinori
中科院分区：
文献类型：
--
作者：
Balamotis, Michael A.;Tamberg, Nele;Kohwi, Yoshinori
学习和记忆等复杂行为与神经元基因表达的快速变化以及随后新突触连接的形成有关。然而，如何处理外部信号以驱动基因表达的特定变化尚不清楚。我们发现基因组组织蛋白 Satb1 在成熟神经元中高度表达，主要在大脑皮层、齿状门和杏仁核中。在 Satb1 缺失的小鼠中，皮质层形态正常。然而，在出生后 Satb1 缺失的皮质锥体神经元中，我们发现树突棘的密度大幅下降，而树突棘在突触传递和可塑性中发挥着关键作用。此外，我们发现在大脑皮层中，Satb1 与多个立即早期基因 (IEG)（Fos、Fosb、Egr1、Egr2、Arc 和 Bdnf）和其他关键神经元基因的基因组位点结合，其中许多基因与突触可塑性有关。 Satb1 的缺失导致出生后早期大脑皮质发育期间以及皮质器官培养物刺激时这些 IEG 的时间和表达水平发生极大改变。这些数据表明 Satb1 对于 LEG 表达的适当时间动态是必需的。基于这些发现，我们提出 Satb1 在皮质神经元中发挥着关键作用，以促进神经元可塑性。
Complex behaviors, such as learning and memory, are associated with rapid changes in gene expression of neurons and subsequent formation of new synaptic connections. However, how external signals are processed to drive specific changes in gene expression is largely unknown. We found that the genome organizer protein Satb1 is highly expressed in mature neurons, primarily in the cerebral cortex, dentate hilus, and amygdala. In Satb1-null mice, cortical layer morphology was normal. However, in postnatal Satb1-null cortical pyramidal neurons, we found a substantial decrease in the density of dendritic spines, which play critical roles in synaptic transmission and plasticity. Further, we found that in the cerebral cortex, Satb1 binds to genomic loci of multiple immediate early genes (IEGs) (Fos, Fosb, Egr1, Egr2, Arc, and Bdnf) and other key neuronal genes, many of which have been implicated in synaptic plasticity. Loss of Satb1 resulted in greatly alters timing and expression levels of these IEGs during early postnatal cerebral cortical development and also upon stimulation in cortical organotypic cultures. These data indicate that Satb1 is required for proper temporal dynamics of LEG expression. Based on these findings, we propose that Satb1 plays a critical role in cortical neurons to facilitate neuronal plasticity.