Friocourt Gaëlle, Poirier Karine, Rakić Sonja, Parnavelas John G, Chelly Jamel
Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK.
Eur J Neurosci. 2006 Feb;23(4):869-76. doi: 10.1111/j.1460-9568.2006.04629.x.
The ARX protein (encoded by the aristaless-related homeobox gene) is a member of the paired class of homeoproteins. More precisely, it is a member of the Aristaless subclass of proteins with a glutamine residue (Q) at the critical position 50 of the homeodomain (Q50). Through identification of diverse inherited or de novo mutations, genetic investigations of X-linked mental retardation conditions have demonstrated the implication of ARX in a wide spectrum of disorders extending from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild forms of X-linked mental retardation without apparent brain abnormalities. These investigations have recently directed attention to the role of this gene in brain development. Analysis of its spatiotemporal localization profile have revealed expression mainly in telencephalic structures at all stages of development. Interestingly, in adult, ARX expression becomes restricted to a population of GABAergic neurons. Although the identification of the target genes regulated by ARX remains a crucial step to better understanding its role during brain development, studies of the role of ARX orthologs in different models have indicated that it is essential for important developmental processes such as proliferation, cell differentiation and neuronal migration.
ARX蛋白（由无耳相关同源框基因编码）是配对类同源结构域蛋白的成员。更确切地说，它是在同源结构域关键位置50（Q50）具有谷氨酰胺残基（Q）的无耳亚类蛋白的成员。通过鉴定各种遗传或新生突变，对X连锁智力迟钝病症的遗传学研究表明，ARX参与了从严重神经元迁移缺陷（如无脑回畸形）到无明显脑异常的轻度X连锁智力迟钝等广泛的病症。这些研究最近将注意力转向了该基因在脑发育中的作用。对其时空定位图谱的分析表明，它主要在发育各阶段的端脑结构中表达。有趣的是，在成体中，ARX的表达局限于一群GABA能神经元。尽管鉴定受ARX调控的靶基因仍然是更好地理解其在脑发育过程中作用的关键一步，但对不同模型中ARX直系同源物作用的研究表明，它对增殖、细胞分化和神经元迁移等重要发育过程至关重要。
