Institute of Zoology, University of Hohenheim, Stuttgart, Baden-Württemberg, Germany.
PLoS One. 2013 Sep 13;8(9):e73646. doi: 10.1371/journal.pone.0073646. eCollection 2013.
Breakage of bilateral symmetry in amphibian embryos depends on the development of a ciliated epithelium at the gastrocoel roof during early neurulation. Motile cilia at the gastrocoel roof plate (GRP) give rise to leftward flow of extracellular fluids. Flow is required for asymmetric gene expression and organ morphogenesis. Wnt signaling has previously been involved in two steps, Wnt/ß-catenin mediated induction of Foxj1, a regulator of motile cilia, and Wnt/planar cell polarity (PCP) dependent cilia polarization to the posterior pole of cells. We have studied Wnt11b in the context of laterality determination, as this ligand was reported to activate canonical and non-canonical Wnt signaling. Wnt11b was found to be expressed in the so-called superficial mesoderm (SM), from which the GRP derives. Surprisingly, Foxj1 was only marginally affected in loss-of-function experiments, indicating that another ligand acts in this early step of laterality specification. Wnt11b was required, however, for polarization of GRP cilia and GRP morphogenesis, in line with the known function of Wnt/PCP in cilia-driven leftward flow. In addition Xnr1 and Coco expression in the lateral-most GRP cells, which sense flow and generate the first asymmetric signal, was attenuated in morphants, involving Wnt signaling in yet another process related to symmetry breakage in Xenopus.
两栖动物胚胎的左右对称性的破坏取决于早期神经胚形成过程中胃腔顶的纤毛上皮的发育。胃腔顶盘(GRP)上的运动纤毛产生细胞外液的左向流动。流动对于不对称基因表达和器官形态发生是必需的。Wnt 信号转导以前曾涉及两个步骤,Wnt/β-catenin 介导的 Foxj1 表达,Foxj1 是运动纤毛的调节因子,以及 Wnt/平面细胞极性(PCP)依赖性纤毛极化到细胞的后极。我们研究了 Wnt11b 在左右决定中的作用,因为据报道该配体可以激活经典和非经典 Wnt 信号转导。发现 Wnt11b 在所谓的浅真皮层(SM)中表达,GRP 来源于该层。令人惊讶的是,在功能丧失实验中 Foxj1 仅受到轻微影响,表明另一种配体在左右特化的这个早期步骤中起作用。然而,Wnt11b 是 GRP 纤毛极化和 GRP 形态发生所必需的,这与 Wnt/PCP 在纤毛驱动的左向流动中的已知功能一致。此外,在形态发生剂中,对流动敏感并产生第一个不对称信号的最外侧 GRP 细胞中的 Xnr1 和 Coco 表达减弱,这涉及到 Wnt 信号转导在与 Xenopus 中对称性破坏相关的另一个过程中。