Gobius Ilan, Morcom Laura, Suárez Rodrigo, Bunt Jens, Bukshpun Polina, Reardon William, Dobyns William B, Rubenstein John L R, Barkovich A James, Sherr Elliott H, Richards Linda J
Queensland Brain Institute, The University of Queensland, St. Lucia, QLD 4072, Australia.
Queensland Brain Institute, The University of Queensland, St. Lucia, QLD 4072, Australia.
Cell Rep. 2016 Oct 11;17(3):735-747. doi: 10.1016/j.celrep.2016.09.033.
The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.
胼胝体是连接并整合两个大脑半球神经活动的主要轴突束。尽管约每4000名儿童中就有1名出生时患有胼胝体发育不全，但这种病症的主要病因仍不清楚。在此，我们证明胼胝体轴突的中线交叉依赖于中间大脑半球间裂的先前重塑和降解。这一重塑事件由大脑半球间裂两侧的星形胶质细胞启动，它们相互嵌入并降解中间的软脑膜。然后，胼胝体轴突优先在这些特殊的星形胶质细胞上延伸以穿过中线。大脑半球间重塑的一个关键调控步骤是这些星形胶质细胞从放射状胶质细胞分化而来，这是由Fgf8信号传导至下游Nfi转录因子启动的。至关重要的是，我们从人类神经影像学研究中获得的结果表明，大脑半球间重塑的发育缺陷很可能是人类胼胝体发育不全的主要病因。
