Rostrocaudal Areal Patterning of Human PSC-Derived Cortical Neurons by FGF8 Signaling.
Rostrocaudal Areal Patterning of Human PSC-Derived Cortical Neurons by FGF8 Signaling.
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DOI：
10.1523/eneuro.0368-17.2018
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发表时间：
2018-03
期刊：
影响因子：
3.4
通讯作者：
Okano H
中科院分区：
文献类型：
--
作者：
Imaizumi K;Fujimori K;Ishii S;Otomo A;Hosoi Y;Miyajima H;Warita H;Aoki M;Hadano S;Akamatsu W;Okano H
大脑皮层被细分为具有特定功能的不同区域。成纤维细胞生长因子8（FGF 8）信号传导的吻尾（R-C）梯度在神经发育期间定义了这种区域身份。在这项研究中，我们概括了人类多能干细胞（PSC）培养的皮质R-C模式。FGF 8信号的调节适当地调节了R-C标记，并且全局基因表达的模式与人类胎儿大脑相应区域的模式相似。此外，我们证明了该培养系统在模拟肌萎缩侧索硬化症（ALS）的区域特异性前脑表型[假定上运动神经元（UMN）表型]中的实用性。我们预计，我们的培养系统将有助于人类神经发育和神经疾病建模的研究。
The cerebral cortex is subdivided into distinct areas that have particular functions. The rostrocaudal (R-C) gradient of fibroblast growth factor 8 (FGF8) signaling defines this areal identity during neural development. In this study, we recapitulated cortical R-C patterning in human pluripotent stem cell (PSC) cultures. Modulation of FGF8 signaling appropriately regulated the R-C markers, and the patterns of global gene expression resembled those of the corresponding areas of human fetal brains. Furthermore, we demonstrated the utility of this culture system in modeling the area-specific forebrain phenotypes [presumptive upper motor neuron (UMN) phenotypes] of amyotrophic lateral sclerosis (ALS). We anticipate that our culture system will contribute to studies of human neurodevelopment and neurological disease modeling.