Neural Progenitor Cells Undergoing Yap/Tead-Mediated Enhanced Self-Renewal Form Heterotopias More Easily in the Diencephalon than in the Telencephalon.
Neural Progenitor Cells Undergoing Yap/Tead-Mediated Enhanced Self-Renewal Form Heterotopias More Easily in the Diencephalon than in the Telencephalon.
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DOI：
10.1007/s11064-017-2390-x
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发表时间：
2018-01
影响因子：
4.4
通讯作者：
Miyata T
中科院分区：
文献类型：
--
作者：
Saito K;Kawasoe R;Sasaki H;Kawaguchi A;Miyata T
细胞的时空有序产生对于大脑发育至关重要。正常情况下，大多数未分化的神经祖细胞（NPC）面向胚胎脑壁的顶端（脑室）表面。NPC从顶面的病理性脱离及其侵入外部神经元区域，即，NPC形成异位，可扰乱大脑的整体结构。虽然NPC异位先前已在各种实验环境中观察到，但其潜在机制在很大程度上仍然未知。是相关蛋白1（Yap 1）和TEA结构域（Tead）蛋白，其作用于Hippo信号传导的下游，增强NPC的干细胞样特征。神经管（未来的脊髓）中Yap 1或Tead的表达升高诱导大规模NPC异位，但雅普/Tead诱导的发育中的脑中NPC的扩增以前没有报道产生NPC异位。为了确定NPC异位是否以区域性特征的方式发生，我们通过子宫内电穿孔将Yap 1-S112 A或Tead-VP 16引入胚胎第10天小鼠端脑和间脑的NPC中，这两个相邻但不同的前脑区域，并比较NPC异位的形成。虽然在这两个地区的NPC表现出增强干样行为，异位更大，更频繁的间脑比端脑。这一结果是雅普/Tead诱导的NPC异位在前脑中的第一个例子，揭示了雅普/Tead诱导的NPC异位并不特异于神经管，也表明这种现象取决于区域因素，如这些细胞的三维几何形状和组装。
Spatiotemporally ordered production of cells is essential for brain development. Normally, most undifferentiated neural progenitor cells (NPCs) face the apical (ventricular) surface of embryonic brain walls. Pathological detachment of NPCs from the apical surface and their invasion of outer neuronal territories, i.e., formation of NPC heterotopias, can disrupt the overall structure of the brain. Although NPC heterotopias have previously been observed in a variety of experimental contexts, the underlying mechanisms remain largely unknown. Yes-associated protein 1 (Yap1) and the TEA domain (Tead) proteins, which act downstream of Hippo signaling, enhance the stem-like characteristics of NPCs. Elevated expression of Yap1 or Tead in the neural tube (future spinal cord) induces massive NPC heterotopias, but Yap/Tead-induced expansion of NPCs in the developing brain has not been previously reported to produce NPC heterotopias. To determine whether NPC heterotopias occur in a regionally characteristic manner, we introduced the Yap1-S112A or Tead-VP16 into NPCs of the telencephalon and diencephalon, two neighboring but distinct forebrain regions, of embryonic day 10 mice by in utero electroporation, and compared NPC heterotopia formation. Although NPCs in both regions exhibited enhanced stem-like behaviors, heterotopias were larger and more frequent in the diencephalon than in the telencephalon. This result, the first example of Yap/Tead-induced NPC heterotopia in the forebrain, reveals that Yap/Tead-induced NPC heterotopia is not specific to the neural tube, and also suggests that this phenomenon depends on regional factors such as the three-dimensional geometry and assembly of these cells.
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影响因子：
5.5
作者：
Nagasaka A;Shinoda T;Kawaue T;Suzuki M;Nagayama K;Matsumoto T;Ueno N;Kawaguchi A;Miyata T
通讯作者：
Miyata T
影响因子：
64.5
作者：
CHENN, A;MCCONNELL, SK
通讯作者：
MCCONNELL, SK
影响因子：
64.5
作者：
Lui JH;Hansen DV;Kriegstein AR
通讯作者：
Kriegstein AR
DOI：
10.1093/brain/aws019
发表时间：
2012-05
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Barkovich AJ;Guerrini R;Kuzniecky RI;Jackson GD;Dobyns WB
通讯作者：
Dobyns WB
影响因子：
5.3
作者：
Miyata T;Okamoto M;Shinoda T;Kawaguchi A
通讯作者：
Kawaguchi A