Hox genes control vertebrate body elongation by collinear Wnt repression.
Hox genes control vertebrate body elongation by collinear Wnt repression.
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DOI：
10.7554/elife.04379
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发表时间：
2015-02-26
期刊：
影响因子：
7.7
通讯作者：
Pourquié O
中科院分区：
文献类型：
--
作者：
Denans N;Iimura T;Pourquié O
在脊椎动物中，脊椎骨的总数是精确定义的。椎体来源于胚胎体，胚胎体在身体形成过程中由体前中胚层（PSM）不断向后产生。我们发现，在鸡胚中，尾芽中后Hox基因（类似物9-13）的激活与轴伸长的减慢有关。我们的数据表明，在椎体前体中共线激活的一组逐渐增加的后侧Hox基因，随着强度的增加而抑制Wnt活性。这导致Brachyury/T转录因子的逐渐抑制，减少中胚层的侵入并减缓伸长过程。由于some some形成的持续，这一机制导致PSM尺寸逐渐减小。这最终导致维甲酸（RA）产生的分节区域靠近尾芽，可能导致分节终止和轴伸长。在人类和其他脊椎动物中，脊柱中骨头（椎骨）的数量在发育早期就确定了。椎骨是由被称为体体的组织块形成的，这些组织块沿着身体轴形成片段——这是一条从胚胎头部到尾部的虚拟线。体体随着胚胎长度的增加而形成，新的体体在胚胎尾部附近周期性地形成。一个被称为Hox基因的基因家族参与控制体的形成。然而，尚不清楚它们是否直接控制形成的体的数量，或者它们是否控制胚胎体的长度。Denans等人研究了鸡胚胎中的Hox基因。实验表明，在胚胎尾端发现的尾芽结构中，一些Hox基因的激活减缓了身体的伸长。Hox基因通过抑制一种称为Wnt的信号通路的活性来实现这一点，因此随着胚胎的发育，尾芽中的Wnt活性逐渐降低。当尾芽中一种叫做视黄酸的分子水平增加时，身体的伸长就停止了，这会导致制造体体所需的干细胞的损失。Denans等人的研究结果表明，Hox基因影响断裂停止的时间，这反过来又对确定形成的体的总数很重要。了解Hox基因如何控制组成体的细胞的形成并影响Wnt信号是未来的主要挑战。DOI: http://dx.doi.org/10.7554/eLife.04379.002
In vertebrates, the total number of vertebrae is precisely defined. Vertebrae derive from embryonic somites that are continuously produced posteriorly from the presomitic mesoderm (PSM) during body formation. We show that in the chicken embryo, activation of posterior Hox genes (paralogs 9–13) in the tail-bud correlates with the slowing down of axis elongation. Our data indicate that a subset of progressively more posterior Hox genes, which are collinearly activated in vertebral precursors, repress Wnt activity with increasing strength. This leads to a graded repression of the Brachyury/T transcription factor, reducing mesoderm ingression and slowing down the elongation process. Due to the continuation of somite formation, this mechanism leads to the progressive reduction of PSM size. This ultimately brings the retinoic acid (RA)-producing segmented region in close vicinity to the tail bud, potentially accounting for the termination of segmentation and axis elongation. DOI: http://dx.doi.org/10.7554/eLife.04379.001 In humans and other vertebrates, the number of bones (vertebrae) in the spine is determined early in development. The vertebrae form from blocks of tissue called somites that make segments along the body axis—a virtual line running from the head to the tail-end—of the embryo. The somites form as the embryo increases in length, with new somites forming periodically at the back near the embryo's tail-end. A family of genes called the Hox genes are involved in controlling the formation of the somites. However, it is not known whether they directly control the number of somites that form, or whether they control the length of the body of the embryo. Denans et al. studied the Hox genes in chicken embryos. The experiments suggest that the activation of some of the Hox genes in a structure called the tail-bud, which is found at the tail-end of the embryo, slow down the elongation of the body. The Hox genes achieve this by repressing the activity of a signaling pathway called Wnt so that Wnt activity in the tail-bud progressively decreases as the embryo develops. The elongation of the body stops when the levels of a molecule called retinoic acid increase in the tail-bud, which causes the loss of the stem cells that are needed to make the somites. Denans et al.'s findings suggest that Hox genes influence the timing of the halt in elongation, which in turn is important for determining the total number of somites that form. Understanding how Hox genes control the formation of the cells that will make up the somites and influence Wnt signaling is a major challenge for the future. DOI: http://dx.doi.org/10.7554/eLife.04379.002