Abstract
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.
Highlights
In vertebrates many inner organs of the chest and abdomen, such as heart and stomach, are asymmetrically localized along the left-right (LR) body axis [1]
Wnt11b is Expressed in the Superficial Mesoderm As a first step to elucidate the role of Wnt11b during LR axis development we analyzed mRNA expression patterns at LR relevant sites (Figure 1A–D)
In dorsal regions the expression remained restricted to the superficial mesoderm (SM), while mRNA in more lateral and ventral regions was detected in deep mesodermal cells as well (Figure 1B9)
Summary
In vertebrates many inner organs of the chest and abdomen, such as heart and stomach, are asymmetrically localized along the left-right (LR) body axis [1]. The non-canonical Wnt/ PCP pathway was shown to be necessary for cilia polarization to the posterior pole of GRP cells [21], as a prerequisite for the generation of a directed laminar flow from right to left [16,22]. This role of Wnt/PCP for LR axis specification was described in mouse [23,24], arguing for evolutionary conservation of this Wnt-dependent step in LR development as well
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