Assembly of functionally integrated human forebrain spheroids.
Assembly of functionally integrated human forebrain spheroids.
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DOI：
10.1038/nature22330
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发表时间：
2017-05-04
期刊：
影响因子：
64.8
通讯作者：
Paşca SP
中科院分区：
文献类型：
--
作者：
Birey F;Andersen J;Makinson CD;Islam S;Wei W;Huber N;Fan HC;Metzler KRC;Panagiotakos G;Thom N;O'Rourke NA;Steinmetz LM;Bernstein JA;Hallmayer J;Huguenard JR;Paşca SP
神经系统的发育涉及一系列协调的事件，包括GABA能神经元从腹侧前脑迁移到背侧前脑及其整合到皮质回路中。然而，这些区域间的相互作用尚未与人类细胞建模。在这里，我们从人类多能细胞生成三维球体，类似于背侧或腹侧前脑，并含有皮质神经元或GABA能神经元。这些亚结构域特异性的前脑球状体可以组装成类似于胎儿前脑迁移的中间神经元跳跃式迁移。使用这个系统，我们发现，在蒂莫西综合征-一种神经发育障碍，是由CaV1.2钙通道突变引起的，中间神经元显示异常迁移突变。我们还表明，迁移后，interneurons功能整合与海马神经元，形成一个微生理系统。我们预计，这种方法将有助于研究发育和疾病，并获得类似于其他大脑区域的球体，以在体外组装电路。
The development of the nervous system involves a coordinated succession of events including the migration of GABAergic neurons from ventral to dorsal forebrain and their integration into cortical circuits. However, these interregional interactions have not yet been modelled with human cells. Here, we generate from human pluripotent cells three-dimensional spheroids resembling either the dorsal or ventral forebrain and containing cortical glutamatergic or GABAergic neurons. These subdomain-specific forebrain spheroids can be assembled to recapitulate the saltatory migration of interneurons similar to migration in fetal forebrain. Using this system, we find that in Timothy syndrome– a neurodevelopmental disorder that is caused by mutations in the CaV1.2 calcium channel, interneurons display abnormal migratory saltations. We also show that after migration, interneurons functionally integrate with glutamatergic neurons to form a microphysiological system. We anticipate that this approach will be useful for studying development and disease, and for deriving spheroids that resemble other brain regions to assemble circuits in vitro.
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影响因子：
25
作者：
Krey, Jocelyn F.;Pasca, Sergiu P.;Shcheglovitov, Aleksandr;Yazawa, Masayuki;Schwemberger, Rachel;Rasmusson, Randall;Dolmetsch, Ricardo E.
通讯作者：
Dolmetsch, Ricardo E.
影响因子：
64.8
作者：
Lui, Jan H.;Nowakowski, Tomasz J.;Pollen, Alex A.;Javaherian, Ashkan;Kriegstein, Arnold R.;Oldham, Michael C.
通讯作者：
Oldham, Michael C.
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.1013494107
发表时间：
2010-11-02
影响因子：
11.1
作者：
Mao, Lifang;Takamiya, Kogo;Huganir, Richard L.
通讯作者：
Huganir, Richard L.
影响因子：
16.2
作者：
Micheva, Kristina D.;Busse, Brad;Weiler, Nicholas C.;O'Rourke, Nancy;Smith, Stephen J.
通讯作者：
Smith, Stephen J.