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首页> 外文期刊>Cell Reports >Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes
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Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes

机译：Chx10通过两种不同的基因抑制模式巩固V2a Interneuron身份。

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During development, two cell types born from closely related progenitor pools often express identical transcriptional regulators despite their completely distinct characteristics. This phenomenon implies the need for a mechanism that operates to segregate the identities of the two cell types throughout differentiation after initial fate commitment. To understand this mechanism, we investigated the fate specification of spinal V2a interneurons, which share important developmental genes with motor neurons (MNs). We demonstrate that the paired homeodomain factor Chx10 functions as a critical determinant for V2a fate and is required to consolidate V2a identity in postmitotic neurons. Chx10 actively promotes V2a fate, downstream of the LIM-homeodomain factor Lhx3, while concomitantly suppressing the MN developmental program by preventing the MN-specific transcription complex from binding and activating MN genes. This dual activity enables Chx10 to effectively separate the V2a and MN pathways. Our study uncovers a widely applicable gene regulatory principle for segregating related cell fates.
机译：在发育过程中，密切相关的祖细胞所产生的两种细胞类型尽管具有完全不同的特征，却通常表达相同的转录调节因子。这种现象意味着需要一种机制，该机制可以在最初的命运承诺后的整个分化过程中分离两种细胞类型的身份。为了了解这种机制，我们研究了脊髓V2a中间神经元的命运规范，该神经元与运动神经元（MN）共享重要的发育基因。我们证明配对的同源域因子Chx10充当V2a命运的关键决定因素，并且是巩固有丝分裂后神经元中V2a身份所必需的。 Chx10积极促进LIM-同源结构域因子Lhx3下游的V2a命运，同时通过阻止MN特异性转录复合物结合和激活MN基因来抑制MN发育程序。这种双重活性使Chx10能够有效分离V2a和MN途径。我们的研究发现了分离相关细胞命运的广泛适用的基因调控原理。

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