Identification of Arx targets unveils new candidates for controlling cortical interneuron migration and differentiation.
Identification of Arx targets unveils new candidates for controlling cortical interneuron migration and differentiation.
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DOI：
10.3389/fncel.2011.00028
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发表时间：
2011
影响因子：
5.3
通讯作者：
Parnavelas JG
中科院分区：
文献类型：
--
作者：
Friocourt G;Parnavelas JG
同源盒转录因子ARX的突变被发现与一系列疾病有关，从具有严重神经元迁移缺陷的表型，如无脑畸形，到没有明显大脑异常的轻度智能障碍，但与肌张力障碍和癫痫相关。ARX的表达主要局限于含有GABA的神经元群体。对ARX功能丧失的影响的研究，无论是在人类还是在突变的小鼠中，都发现了不同程度的缺陷，表明该基因在脑模式、神经元增殖和迁移、细胞成熟和分化以及轴突生长和连通性方面发挥着多种作用。然而，到目前为止，人们对Arx作为转录因子的功能以及它结合和调节哪些基因知之甚少。最近，我们将染色质免疫沉淀和mRNA表达与微阵列分析相结合，在转基因神经母细胞瘤N2a细胞和小鼠胚胎脑中鉴定了约1000个Arx结合的基因启动子。为了将ARx靶标的分析范围缩小到那些最有可能控制皮质神经元间迁移和/或分化的基因，我们在这里将我们的数据与之前发表的研究进行比较，以寻找E13.5和E15.5之间的皮质间神经元中丰富或下调的基因。因此，我们在皮质迁移神经元中发现了14个Arx靶基因(CXCR7、Meis1、PPap2a、SLC12a5、Ets2、Phlda1、Egr1、Igf1、Lmo3、Sema6、Lgi1、ALK、TGFB3和Napb)和5个特异下调的基因(Hmgn3、Lmo1、EBF3、Rasgef1b和Slit2)。在这篇综述中，我们介绍了这些基因，并讨论了Arx对它们的可能调节可能导致GABA能神经元的功能障碍，从而导致智力低下和癫痫。
Mutations in the homeobox transcription factor ARX have been found to be responsible for a wide spectrum of disorders extending from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild forms of intellectual disabilities without apparent brain abnormalities, but with associated features of dystonia and epilepsy. Arx expression is mainly restricted to populations of GABA-containing neurons. Studies of the effects of ARX loss of function, either in humans or mutant mice, revealed varying defects, suggesting multiple roles of this gene in brain patterning, neuronal proliferation and migration, cell maturation and differentiation, as well as axonal outgrowth and connectivity. However, to date, little is known about how Arx functions as a transcription factor or which genes it binds and regulates. Recently, we combined chromatin immunoprecipitation and mRNA expression with microarray analysis and identified approximately 1000 gene promoters bound by Arx in transfected neuroblastoma N2a cells and mouse embryonic brain. To narrow the analysis of Arx targets to those most likely to control cortical interneuron migration and/or differentiation, we compare here our data to previously published studies searching for genes enriched or down-regulated in cortical interneurons between E13.5 and E15.5. We thus identified 14 Arx-target genes enriched (Cxcr7, Meis1, Ppap2a, Slc 12a5, Ets2, Phlda1, Egr1, Igf1, Lmo3, Sema6, Lgi1, Alk, Tgfb3, and Napb) and 5 genes specifically down-regulated (Hmgn3, Lmo1, Ebf3, Rasgef1b, and Slit2) in cortical migrating neurons. In this review, we present these genes and discuss how their possible regulation by Arx may lead to the dysfunction of GABAergic neurons, resulting in mental retardation and epilepsy.
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影响因子：
2.5
作者：
Colombo, E;Galli, R;Broccoli, V
通讯作者：
Broccoli, V
影响因子：
3.5
作者：
Di Cristo, G.
通讯作者：
Di Cristo, G.
DOI：
10.1097/01.jnen.0000182978.56612.41
发表时间：
2005-10-01
影响因子：
3.2
作者：
Forman, MS;Squier, W;Golden, JA
通讯作者：
Golden, JA
影响因子：
2.5
作者：
Faux, Clare;Rakic, Sonja;Parnavelas, John G.
通讯作者：
Parnavelas, John G.
DOI：
10.1111/j.1460-9568.2011.07896.x
发表时间：
2011-11
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Antypa M;Faux C;Eichele G;Parnavelas JG;Andrews WD
通讯作者：
Andrews WD