Retinoic acid signaling organizes endodermal organ specification along the entire antero-posterior axis.
Retinoic acid signaling organizes endodermal organ specification along the entire antero-posterior axis.
复制标题
DOI：
10.1371/journal.pone.0005845
复制
发表时间：
2009-06-10
期刊：
影响因子：
3.7
通讯作者：
Grapin-Botton A
中科院分区：
文献类型：
--
作者：
Bayha E;Jørgensen MC;Serup P;Grapin-Botton A
在羊膜中，内胚层器官原基在原肠形成和肠管折叠之间具体化。尽管已确定少数个别内胚层器官发育所需的RA信号，但在该胚层中尚未对其在整个前后轴上的活性进行系统的评估。RA是在靠近发育中的肠管的中胚层从原肠发育到体细胞发生的过程中合成的。在颧弓区域，RA信号控制器官边界的特定水平。在没有RA信号的情况下，形成甲状腺的最前内胚层是明确的。增加前颧弓的RA会导致甲状腺原基的抑制和更多的后部标志物的诱导，如鳃弓HOX基因。相反，减少RA信号会使内胚层中的HOX基因向后移动。这些结果表明，RA在咽内胚层中以一种分级的方式发挥尾状因子的作用。前肠后段和中肠器官原基也需要RA，但将内胚层暴露于额外的RA并不足以使这些原基向前扩展。我们发现，与非羊膜相比，在雏鸡中，RA信号不仅在原肠发育过程中是必需的，而且在体细胞发生过程中也是整个肠管折叠所必需的。我们的结果表明，中肠标志物CDxA的诱导和胰腺的诱导需要内胚层直接的RA信号。此外，CDxA+细胞之间的通讯对于维持CDxA的表达是必要的，从而使中肠原基的细胞同步。我们进一步证明，RA途径与FGF4在内胚层构型中起协同作用，而不是介导FGF4的活性。我们的工作证实，维甲酸(RA)信号在鸡胚胎中协调不同内胚层器官沿前后轴的位置，并可作为从ES细胞分化特定内胚层器官的基础。
Endoderm organ primordia become specified between gastrulation and gut tube folding in Amniotes. Although the requirement for RA signaling for the development of a few individual endoderm organs has been established a systematic assessment of its activity along the entire antero-posterior axis has not been performed in this germ layer. RA is synthesized from gastrulation to somitogenesis in the mesoderm that is close to the developing gut tube. In the branchial arch region specific levels of RA signaling control organ boundaries. The most anterior endoderm forming the thyroid gland is specified in the absence of RA signaling. Increasing RA in anterior branchial arches results in thyroid primordium repression and the induction of more posterior markers such as branchial arch Hox genes. Conversely reducing RA signaling shifts Hox genes posteriorly in endoderm. These results imply that RA acts as a caudalizing factor in a graded manner in pharyngeal endoderm. Posterior foregut and midgut organ primordia also require RA, but exposing endoderm to additional RA is not sufficient to expand these primordia anteriorly. We show that in chick, in contrast to non-Amniotes, RA signaling is not only necessary during gastrulation, but also throughout gut tube folding during somitogenesis. Our results show that the induction of CdxA, a midgut marker, and pancreas induction require direct RA signaling in endoderm. Moreover, communication between CdxA + cells is necessary to maintain CdxA expression, therefore synchronizing the cells of the midgut primordium. We further show that the RA pathway acts synergistically with FGF4 in endoderm patterning rather than mediating FGF4 activity. Our work establishes that retinoic acid (RA) signaling coordinates the position of different endoderm organs along the antero-posterior axis in chick embryos and could serve as a basis for the differentiation of specific endodermal organs from ES cells.
登录
查看更多内容
影响因子：
11.8
作者：
Guris, DL;Duester, G;Imamoto, A
通讯作者：
Imamoto, A
影响因子：
2.5
作者：
Blentic, A;Gale, E;Maden, M
通讯作者：
Maden, M
影响因子：
4.6
作者：
Halilagic, A;Zile, MH;Studer, M
通讯作者：
Studer, M
影响因子：
2.7
作者：
Chen, YL;Pan, FC;Pieler, T
通讯作者：
Pieler, T
影响因子：
3.2
作者：
Ahnfelt-Ronne, Jonas;Jorgensen, Mette C.;Hecksher-Sorensen, Jacob
通讯作者：
Hecksher-Sorensen, Jacob