Interneuron Origins in the Embryonic Porcine Medial Ganglionic Eminence
Interneuron Origins in the Embryonic Porcine Medial Ganglionic Eminence
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DOI：
10.1523/jneurosci.2738-20.2021
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发表时间：
2021-04-07
影响因子：
5.3
通讯作者：
Baraban, Scott C.
中科院分区：
文献类型：
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作者：
Casalia, Mariana L.;Li, Tina;Baraban, Scott C.
中间神经元有助于神经回路的复杂性和维持正常的脑功能。啮齿动物的中间神经元起源于胚胎神经节突起，但其他物种的发育起源尚不清楚。在这里，我们发现转录因子在猪胚胎皮层下的表达模式与啮齿类动物相似，描绘了一个独特的内侧神经节隆起（MGE）祖域。基于Nkx2.1、Lhx6和Dlx2的表达，体外分化为表达GABA的神经元，以及外植体实验中强大的迁移能力，我们提出皮层和海马中间神经元起源于猪的MGE区。在异种移植到成年雄性和雌性大鼠海马后，我们进一步证明猪MGE祖细胞像啮齿类动物一样迁移并分化为表达GABA的形态不同的中间神经元。我们的研究结果表明，中间神经元发育的基本规则在物种间是保守的，并且猪胚胎MGE祖细胞可以作为基于中间神经元的异种移植治疗的有价值的来源。
Interneurons contribute to the complexity of neural circuits and maintenance of normal brain function. Rodent interneurons originate in embryonic ganglionic eminences, but developmental origins in other species are less understood. Here, we show that transcription factor expression patterns in porcine embryonic subpallium are similar to rodents, delineating a distinct medial ganglionic eminence (MGE) progenitor domain. On the basis of Nkx2.1, Lhx6, and Dlx2 expression, in vitro differentiation into neurons expressing GABA, and robust migratory capacity in explant assays, we propose that cortical and hippocampal interneurons originate from a porcine MGE region. Following xenotransplantation into adult male and female rat hippocampus, we further demonstrate that porcine MGE progenitors, like those from rodents, migrate and differentiate into morphologically distinct interneurons expressing GABA. Our findings reveal that basic rules for interneuron development are conserved across species, and that porcine embryonic MGE progenitors could serve as a valuable source for interneuron-based xenotransplantation therapies.