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首页> 外文期刊>Development >Development of the prethalamus is crucial for thalamocortical projection formation and is regulated by Olig2
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Development of the prethalamus is crucial for thalamocortical projection formation and is regulated by Olig2

机译：丘脑的发育对于丘脑皮质投射形成至关重要，并受Olig2调节

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Thalamocortical axons (TCAs) pass through the prethalamus in the first step of their neural circuit formation. Although it has been supposed that the prethalamus is an intermediate target for thalamocortical projection formation, much less is known about the molecular mechanisms of this targeting. Here, we demonstrated the functional implications of the prethalamus in the formation of this neural circuit. We show that Olig2 transcription factor, which is expressed in the ventricular zone (VZ) of prosomere 3, regulates prethalamus formation, and loss of Olig2 results in reduced prethalamus size in early development, which is accompanied by expansion of the thalamic eminence (TE). Extension of TCAs is disorganized in the Olig2-KO dorsal thalamus, and initial elongation of TCAs is retarded in the Olig2-KO forebrain. Microarray analysis demonstrated upregulation of several axon guidance molecules, including Epha3 and Epha5, in the Olig2-KO basal forebrain. In situ hybridization showed that the prethalamus in the wild type excluded the expression of Epha3 and Epha5, whereas loss of Olig2 resulted in reduction of this Ephas-negative area and the corresponding expansion of the Ephas-positive TE. Dissociated cultures of thalamic progenitor cells demonstrated that substrate-bound EphA3 suppresses neurite extension from dorsal thalamic neurons. These results indicate that Olig2 is involved in correct formation of the prethalamus, which leads to exclusion of the EphA3-expressing region and is crucial for proper TCA formation. Our observation is the first report showing the molecular mechanisms underlying how the prethalamus acts on initial thalamocortical projection formation.
机译：丘脑皮质轴突（TCA）在其神经回路形成的第一步穿过丘脑。尽管据认为丘脑前是丘脑皮质突出物形成的中间靶标，但对这种靶标的分子机理了解甚少。在这里，我们证明了前丘脑在该神经回路形成中的功能含义。我们显示Olig2转录因子，在prosomere 3的心室区（VZ）中表达，调节丘脑前的形成，Olig2的丧失导致丘脑前体大小在早期发育中减少，并伴有丘脑隆起（TE）的扩展。 TCAs的延伸在Olig2-KO背丘脑中杂乱无章，而TCAs的初始延伸在Olig2-KO前脑中被延缓。芯片分析表明，Olig2-KO基底前脑中的几种轴突导向分子（包括Epha3和Epha5）上调。原位杂交表明，野生型前丘脑排除了Epha3和Epha5的表达，而Olig2的缺失导致该Ephas阴性区域的减少和Ephas阳性TE的相应扩展。丘脑祖细胞的分离培养表明，底物结合的EphA3抑制了背丘脑神经元的神经突延伸。这些结果表明，Olig2参与了丘脑前丘脑的正确形成，从而导致EphA3表达区域的排斥，这对于正确的TCA形成至关重要。我们的观察结果是第一个报告，显示了丘脑前部如何作用于丘脑皮质前突形成的分子机制。

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