Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation
Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation
复制标题
DOI：
10.1101/gad.486708
复制
发表时间：
2008-12-01
影响因子：
10.5
通讯作者：
Klein, Ruediger
中科院分区：
文献类型：
--
作者：
Egea, Joaquim;Erlacher, Christian;Klein, Ruediger
在小鼠早期发育过程中，前内脏内胚层（AVE）分泌抑制因子和激活因子信号，这些信号对于胚胎前后轴（AP）的建立以及将中胚层的形成限制在原始条纹（PS）区域的后外胚层至关重要。在这里，我们发现AVE细胞具有额外的形态发生功能。这些细胞表达跨膜蛋白FLRT3。根据Nodal和Wnt的正常表达模式以及外胚层中适当AP模式的建立，FLRT3基因消融未影响AVE的信号功能。然而，FLRT3（-/-）胚胎在AVE区显示高度紊乱的基底膜（BM）。随后，邻近的前外胚层细胞表现出上皮-间充质转化（EMT）样过程，其特征是细胞极性丧失、细胞浸润、EMT和中胚层标记基因Eomes、Brachyury/T和FGF8的上调。这些结果表明，AVE作为一个形态发生边界，通过维持BM的完整性来阻止EMT和中胚层在前外胚层的诱导。我们认为这种新功能与AVE的信号活动合作，限制EMT和中胚层诱导到后外胚层。
During early mouse development, the anterior visceral endoderm (AVE) secretes inhibitor and activator signals that are essential for establishing the anterior-posterior (AP) axis of the embryo and for restricting mesoderm formation to the posterior epiblast in the primitive streak (PS) region. Here we show that AVE cells have an additional morphogenetic function. These cells express the transmembrane protein FLRT3. Genetic ablation of FLRT3 did not affect the signaling functions of the AVE according to the normal expression pattern of Nodal and Wnt and the establishment of a proper AP patterning in the epiblast. However, FLRT3(-/-) embryos showed a highly disorganized basement membrane (BM) in the AVE region. Subsequently, adjacent anterior epiblast cells displayed an epithelial-to-mesenchymal transition (EMT)-like process characterized by the loss of cell polarity, cell ingression, and the up-regulation of the EMT and the mesodermal marker genes Eomes, Brachyury/T, and FGF8. These results suggest that the AVE acts as a morphogenetic boundary to prevent EMT and mesoderm induction in the anterior epiblast by maintaining the integrity of the BM. We propose that this novel function cooperates with the signaling activities of the AVE to restrict EMT and mesoderm induction to the posterior epiblast.