RA-GEF-1 (Rapgef2) is essential for proper development of the midline commissures
RA-GEF-1 (Rapgef2) is essential for proper development of the midline commissures
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DOI：
10.1016/j.neures.2011.08.004
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发表时间：
2011-11-01
影响因子：
2.9
通讯作者：
Kataoka, Tohru
中科院分区：
文献类型：
--
作者：
Bilasy, Shymaa E.;Satoh, Takaya;Kataoka, Tohru
大脑半球由三个主要的半球间纤维直接连接：胼胝体、前连合和海马连合。RA-GEF-1（也称为Rapgef 2）是一种负责Rap 1持续激活的鸟嘌呤核苷酸交换因子。我们以前报告的主要前脑连合在成年背侧端脑特异性RA-GEF-1条件性敲除（cKO）小鼠的解剖缺陷。在这项研究中，我们使用神经解剖追踪和免疫组织化学研究连合纤维的形成在出生后早期的发展。DiI顺行追踪显示cKO小鼠的胼胝体轴突不能穿过中线，从而在同侧形成Probst束，这与皮质中线处缺乏灰盖神经胶质和神经胶质吊带有关。麦胚凝集素结合辣根过氧化物酶逆行追踪证实了cKO小鼠前连合的发育不全，DiI顺行追踪证实了纤维偏离其原始道。海马连合的背侧部发育不全，腹侧部发育不全。这些结果表明RA-GEF-1在大脑中线连合的适当形成中的重要作用。(C)2011 Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
The cerebral hemispheres are directly connected by three major interhemispheric fibers: the corpus callosum, the anterior commissure, and the hippocampal commissure. RA-GEF-1 (also termed Rapgef2) is a guanine nucleotide exchange factor responsible for sustained activation of Rap1. We previously reported anatomical defects of the major forebrain commissures in the adult dorsal telencephalon-specific RA-GEF-1 conditional knockout (cKO) mice. In this study, we use neuroanatomical tracing and immunohistochemistry to study the formation of the commissural fibers during early postnatal development. DiI anterograde tracing reveals the inability of the callosal axons to cross the midline in cKO mice, thereby forming Probst bundles on the ipsilateral side, which is associated with the absence of the indusium griseum glia and the glial sling at the cortical midline. Wheat germ agglutinin-conjugated horseradish peroxidase retrograde tracing verifies the agenesis of the anterior commissure in cKO mice, and DiI anterograde tracing confirms the deviation of the fibers from their original tract. As for the hippocampal commissure, agenesis and hypoplasia are observed in its dorsal and ventral parts, respectively. These results indicate the essential role of RA-GEF-1 in the proper formation of the cerebral midline commissures. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.