Dlx1&2-dependent expression of Zfhx1b (Sip1, Zeb2) regulates the fate switch between cortical and striatal interneurons.

Dlx1&2-dependent expression of Zfhx1b (Sip1, Zeb2) regulates the fate switch between cortical and striatal interneurons.
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Zfhx1b(Sip1、Zeb2)的 Dlx1 和 2 依赖性表达调节皮质和纹状体中间神经元之间的命运转换。

DOI:
10.1016/j.neuron.2012.11.035
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发表时间:
2013-01-09
期刊:
影响因子:
16.2
通讯作者:
Rubenstein JL
Rubenstein JL
中科院分区:
医学1区
文献类型:
--
作者:
McKinsey GL;Lindtner S;Trzcinski B;Visel A;Pennacchio LA;Huylebroeck D;Higashi Y;Rubenstein JL

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哺乳动物的苍白球(皮层和海马)和纹状体中间神经元都产生于胚胎的软腭下,包括内侧神经节隆起(MGE)。在此,我们证明,Zfhx 1b(Sip 1,Zeb 2)锌指同源异型盒基因是必需的MGE,直接下游的Dlx1&2,产生皮质interneurons表达Cxcr 7,MafB和cMaf。在其缺失的情况下,Nkx 2 -1表达不受抑制,并且通常将成为皮质中间神经元的细胞似乎向GABA能纹状体中间神经元的亚型转化。这些结果表明,Zfhx 1b是产生皮质中间神经元所必需的,并提出了Zfhx 1b突变(Mowat-Wilson综合征)人类癫痫的机制。
Mammalian pallial (cortical and hippocampal) and striatal interneurons are both generated in the embryonic subpallium, including the medial ganglionic eminence (MGE). Herein we demonstrate that the Zfhx1b (Sip1, Zeb2) zinc finger homeobox gene is required in the MGE, directly downstream of Dlx1&2, to generate cortical interneurons that express Cxcr7, MafB and cMaf. In its absence, Nkx2-1 expression is not repressed, and cells that ordinarily would become cortical interneurons appear to transform towards a subtype of GABAeric striatal interneurons. These results show that Zfhx1b is required to generate cortical interneurons, and suggest a mechanism for the epilepsy observed in humans with Zfhx1b mutations (Mowat-Wilson syndrome).
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