Wolanski Marian, Khosrowshahian Farhad, Kelly Lisa E, El-Hodiri Heithem M, Crawford Michael J
Department of Biological Sciences, University of Windsor, Windsor, Ontario, Canada.
Genesis. 2009 Jan;47(1):19-31. doi: 10.1002/dvg.20449.
The aristaless-related gene, Arx, plays a fundamental role in patterning the brain in humans and mice. Arx mutants exhibit lissencephaly among other anomalies. We have cloned a Xenopus aristaless homolog that appears to define specific regions of the developing forebrain. xArx2 is transcribed in blastula through neurula stages, and comes to be restricted to the ventral and lateral telencephalon, lateral diencephalon, neural floor plate of the anterior spinal cord, and somites. In this respect, Arx2 expresses in regions similar to Arx with the exception of the somites. Overexpression enlarges the telencephalon, and interference by means of antisense morpholino-mediated translation knockdown reduces growth of this area. Overexpression and inhibition studies demonstrate that misregulation of xArx2 imposes dire consequences upon patterns of differentiation not only in the forebrain where the gene normally expresses, but also in more caudal brain territories and derivatives as well. This suggests that evolutionary changes that expanded Arx-expression from ventral to dorsal prosencephalon might be one of the determinants that marked development and expansion of the telencephalon.
无尾相关基因Arx在人类和小鼠的大脑模式形成中起着重要作用。Arx突变体除了其他异常外还表现出无脑回畸形。我们克隆了一种非洲爪蟾无尾同源物，它似乎定义了发育中的前脑的特定区域。xArx2在囊胚期到神经胚期转录，并逐渐局限于腹侧和外侧端脑、外侧间脑、脊髓前部的神经底板和体节。在这方面，Arx2除了体节外，在与Arx相似的区域表达。过表达会扩大端脑，通过反义吗啉代介导的翻译敲低进行干扰会减少该区域的生长。过表达和抑制研究表明，xArx2的失调不仅会对该基因正常表达的前脑的分化模式产生严重影响，还会对更靠后的脑区及其衍生物产生影响。这表明，将Arx表达从前脑腹侧扩展到背侧的进化变化可能是标志着端脑发育和扩展的决定因素之一。
