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首页> 外文期刊>The European Journal of Neuroscience >Dlx1 transcription factor regulates dendritic growth and postsynaptic differentiation through inhibition of neuropilin-2 and PAK3 expression
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Dlx1 transcription factor regulates dendritic growth and postsynaptic differentiation through inhibition of neuropilin-2 and PAK3 expression

机译:DLX1转录因子通过抑制神经疏素-2和PAK3表达来调节树突生长和突触后分化

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摘要

Dlx1, a member of the homeobox domain transcriptional factors, is expressed in a subset of interneurons and is involved in their differentiation. To understand the roles of Dlx1 in dendritic and postsynaptic differentiation, we manipulated Dlx1 expression in both excitatory pyramidal neurons and inhibitory interneurons in hippocampal culture. Exogenous expression of Dlx1 in pyramidal neurons, which lack endogenous Dlx1, resulted in reduced complexity of dendritic arborization. This effect was dependent on the DNA-binding motif of Dlx1. Dlx1 overexpression also induced prominent reduction of spine density, but with mild suppression in the formation of postsynaptic densities. To confirm the roles of endogenous Dlx1, we knocked down Dlx1 in interneurons and found enhanced dendritic growth. By manipulating the expression of possible downstream effectors of Dlx1, neuropilin-2 and p21-activated kinase 3, we provided evidence for the involvement of these two signaling molecules in Dlx1-dependent regulation of dendritic differentiation. Our experimental data support the idea that Dlx1 expression in developing interneurons specifically suppresses two important downstream regulators, leading to the characteristic morphology of Dlx1-expressing interneurons with less branched dendrites and few dendritic spines.
机译:DLX1是Homeobox结构域转录因子的成员,在中间核的子集中表示,并且参与其分化。为了了解DLX1在树突中的角质和突触后分化,我们在海马培养中操纵DLX1表达和兴奋性锥体神经元和抑制​​性核心。缺乏内源性DLX1的金字塔神经元中DLX1的外源性表达导致树突树突中的复杂性降低。这种效果依赖于DLX1的DNA结合基序。 DLX1过表达也诱导脊柱密度的显着降低,但在形成后突触密度的形成时受到轻度抑制。为了确认内源性DLX1的作用,我们将DLX1击倒了中间核,发现了增强的树突生长。通过操纵DLX1,神经疏松素-2和P21-活化激酶3的可能下游效应器的表达,我们提供了对DLX1依赖性分化的DLX1依赖性调节中这两个信号分子参与的证据。我们的实验数据支持思想,即在发展中间核中的DLX1表达特异性地抑制了两个重要的下游调节因子,导致DLX1表达中间核的特征形态,具有较少的分支枝晶和少数树突刺。

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