The transcription factor Cux2 marks development of an A-delta sublineage of TrkA sensory neurons

The transcription factor Cux2 marks development of an A-delta sublineage of TrkA sensory neurons
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DOI:
10.1016/j.ydbio.2011.09.007
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发表时间:
2011-12-01
影响因子:
2.7
通讯作者:
Ernfors, Patrik
Ernfors, Patrik
中科院分区:
生物学3区
文献类型:
--
作者:
Bachy, Isabelle;Franck, Marina C. M.;Ernfors, Patrik

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胚胎发育过程中产生的许多不同类型的背根神经节(DRG)感觉神经元之间的发育过程和独特的分子同一性为不同的体感知觉方式提供了细胞基础。导致不同类型伤害性感觉神经元产生的机制仍然只有部分了解。在这里,我们证明了转录因子Cux2是由神经营养因子受体TrkA、TrkB和TrkC的表达定义的三个主要亚系感觉神经元亚群的新标记。特别是,它在早期TrkA(+)神经元亚群中表达,这些神经元是在DRG中Ngn1非依赖性启动神经发生的早期出现的。出生后,Cux2标记了一个特定的A-Delta伤害性感受器亚型,如TrkA和NF200的表达,但缺少TRPV1。对Cux2突变小鼠的分析表明,Cux2不是指定Trk(+)神经元亚群所必需的。然而,Cux2突变小鼠对机械刺激敏感,但对冷热刺激不敏感,这与机械感受性神经元回路规范过程中的要求是一致的。因此,我们的结果表明,Cux2是表达的,并且可能参与了特定亚型的髓鞘TrkA(+)伤害性受体的形成。(C)2011 Elsevier Inc.保留所有权利。
The developmental process and unique molecular identity between the many different types of dorsal root ganglion (DRG) sensory neurons generated during embryogenesis provide the cellular basis for the distinct perceptual modalities of somatosensation. The mechanisms leading to the generation of different types of nociceptive sensory neurons remain only partly understood. Here, we show that the transcription factor Cux2 is a novel marker of sensory neuron subpopulations of three main sublineages as defined by the expression of neurotrophic factor receptors TrkA, TrkB and TrkC. In particular, it is expressed in a subpopulation of early TrkA(+) neurons that arise during the early, Ngn1-independent initiated neurogenesis in the DRG. Postnatally, Cux2 marks a specific subtype of A-delta nociceptors as seen by expression of TrkA and NF200 but absence of TrpV1. Analysis of Cux2 mutant mice shows that Cux2 is not required for specification of Trk(+) neuronal subpopulations. However, Cux2 mutant mice are hypersensitive to mechanical, but not to heat or cold stimuli, consistent with a requirement in the process of specification of the mechanoreceptive neuron circuit. Hence, our results show that Cux2 is expressed and may participate in development of a specific subtype of myelinated TrkA(+) nociceptors. (C) 2011 Elsevier Inc. All rights reserved.