Six1 is a key regulator of the developmental and evolutionary architecture of sensory neurons in craniates.
Six1 is a key regulator of the developmental and evolutionary architecture of sensory neurons in craniates.
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DOI：
10.1186/1741-7007-12-40
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发表时间：
2014-05-29
期刊：
影响因子：
5.4
通讯作者：
Kawakami K
中科院分区：
文献类型：
--
作者：
Yajima H;Suzuki M;Ochi H;Ikeda K;Sato S;Yamamura K;Ogino H;Ueno N;Kawakami K
动物的各种感觉和感觉神经结构在适应过程中进化，以利用不同的环境。在颅骨中，躯干感觉系统已经从脊髓（髓内）内的简单机械感觉神经元（称为Rohon-Beard（RB）细胞）进化为脊髓（髓外）外背根神经节（DRG）的多模式感觉神经元。鱼类和两栖类的躯干感觉系统在发育过程中从RB细胞切换到DRG，而蝾螈则完全依赖DRG系统。个体发育转换的机制及其与系统发育转变的联系仍然未知。在非洲爪蟾中，Six 1过表达促进RB细胞的早熟凋亡和髓外感觉神经元的出现，而Six 1敲低延迟RB细胞数量的减少。小鼠中Six 1和Six 4的基因消融导致髓内感觉神经元样细胞的出现，这是神经嵴细胞向脊髓内侧迁移以及产生未成熟DRG神经元和融合DRG的结果。神经嵴线中SIX 1表达的恢复部分挽救了表型，表明正常髓外感觉神经发生的SIX 1细胞自主要求。小鼠Six 1增强子介导的DRG神经元的表达激活非洲爪蟾RB细胞的转录早于内源性Six 1表达，这表明在感觉发育过程中小鼠SIX 1表达的发病早于非洲爪蟾。结果表明Six 1在非洲爪蟾发育过程中RB细胞向DRG神经元的转化和小鼠DRG系统的建立中起着重要作用。该研究提供的证据表明，与小鼠Six 1增强子相关的SIX 1表达的早期出现对于小鼠DRG-显性系统的形成至关重要，表明Six 1增强子序列的异时变化在躯干感觉结构的改变中起重要作用，并有助于躯干感觉系统的进化。
Various senses and sensory nerve architectures of animals have evolved during adaptation to exploit diverse environments. In craniates, the trunk sensory system has evolved from simple mechanosensory neurons inside the spinal cord (intramedullary), called Rohon-Beard (RB) cells, to multimodal sensory neurons of dorsal root ganglia (DRG) outside the spinal cord (extramedullary). The fish and amphibian trunk sensory systems switch from RB cells to DRG during development, while amniotes rely exclusively on the DRG system. The mechanisms underlying the ontogenic switching and its link to phylogenetic transition remain unknown. In Xenopus, Six1 overexpression promoted precocious apoptosis of RB cells and emergence of extramedullary sensory neurons, whereas Six1 knockdown delayed the reduction in RB cell number. Genetic ablation of Six1 and Six4 in mice led to the appearance of intramedullary sensory neuron-like cells as a result of medial migration of neural crest cells into the spinal cord and production of immature DRG neurons and fused DRG. Restoration of SIX1 expression in the neural crest-linage partially rescued the phenotype, indicating the cell autonomous requirements of SIX1 for normal extramedullary sensory neurogenesis. Mouse Six1 enhancer that mediates the expression in DRG neurons activated transcription in Xenopus RB cells earlier than endogenous six1 expression, suggesting earlier onset of mouse SIX1 expression than Xenopus during sensory development. The results indicated the critical role of Six1 in transition of RB cells to DRG neurons during Xenopus development and establishment of exclusive DRG system of mice. The study provided evidence that early appearance of SIX1 expression, which correlated with mouse Six1 enhancer, is essential for the formation of DRG-dominant system in mice, suggesting that heterochronic changes in Six1 enhancer sequence play an important role in alteration of trunk sensory architecture and contribute to the evolution of the trunk sensory system.
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