Nkx2.1-derived astrocytes and neurons together with Slit2 are indispensable for anterior commissure formation.

Nkx2.1-derived astrocytes and neurons together with Slit2 are indispensable for anterior commissure formation.
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DOI:
10.1038/ncomms7887
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发表时间:
2015-04-23
影响因子:
16.6
通讯作者:
Lebrand C
Lebrand C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Minocha S;Valloton D;Ypsilanti AR;Fiumelli H;Allen EA;Yanagawa Y;Marin O;Chédotal A;Hornung JP;Lebrand C

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在中线处和中线周围存在的导柱细胞提供引导信号,通过连合定向生长的轴突。在这里,我们表明已知控制GABA能中间神经元特化的转录因子Nkx2.1也调节小鼠前连合(AC)内星形胶质细胞和多突胶质细胞的分化。Nkx2.1阳性胶质细胞被发现起源于腹侧端脑的三个生发区。在E14.5时,在AC区域内和周围观察到Nkx2.1衍生的神经胶质。此后,选择性细胞消融策略显示出Nkx2.1衍生细胞(GABA能中间神经元和星形胶质细胞)对AC的正确形成的协同作用。最后,我们的研究结果表明,Nkx2.1调节的细胞介导AC轴突的指导,通过表达的排斥线索,Slit2。这些结果带来了有趣的见解中线端脑胶质细胞的空间和时间的起源,并强调了神经元和星形胶质细胞对中线连合形成的重要性。 导柱细胞提供引导线索,定向生长的轴突在大脑中,但鲜为人知的是,中线导柱细胞,填充小鼠前连合(AC)。在这里,作者表明,转录因子Nkx2.1调节星形胶质细胞和神经元的分化,这些神经元通过Slit2的表达合作指导AC轴突。
Guidepost cells present at and surrounding the midline provide guidance cues that orient the growing axons through commissures. Here we show that the transcription factor Nkx2.1 known to control the specification of GABAergic interneurons also regulates the differentiation of astroglia and polydendrocytes within the mouse anterior commissure (AC). Nkx2.1-positive glia were found to originate from three germinal regions of the ventral telencephalon. Nkx2.1-derived glia were observed in and around the AC region by E14.5. Thereafter, a selective cell ablation strategy showed a synergistic role of Nkx2.1-derived cells, both GABAergic interneurons and astroglia, towards the proper formation of the AC. Finally, our results reveal that the Nkx2.1-regulated cells mediate AC axon guidance through the expression of the repellent cue, Slit2. These results bring forth interesting insights about the spatial and temporal origin of midline telencephalic glia, and highlight the importance of neurons and astroglia towards the formation of midline commissures. Guidepost cells provide guidance cues that orient growing axons in the brain but little is known about the midline guidepost cells that populate the mouse anterior commissure (AC). Here, the authors show that the transcription factor Nkx2.1 regulates the differentiation of astroglia and neurons that cooperate to guide AC axons through the expression of Slit2.
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