Canonical Wnt signaling in the visceral muscle is required for left–right asymmetric development of the Drosophila midgut

Abstract

Many animals develop left-right (LR) asymmetry in their internal organs. The mechanisms of LR asymmetric development are evolutionarily divergent, and are poorly understood in invertebrates. Therefore, we studied the genetic pathway of LR asymmetric development in Drosophila. Drosophila has several organs that show directional and stereotypic LR asymmetry, including the embryonic gut, which is the first organ to develop LR asymmetry during Drosophila development. In this study, we found that genes encoding components of the Wnt-signaling pathway are required for LR asymmetric development of the anterior part of the embryonic midgut (AMG). frizzled 2 (fz2) and Wnt4, which encode a receptor and ligand of Wnt signaling, respectively, were required for the LR asymmetric development of the AMG. arrow (arr), an ortholog of the mammalian gene encoding low-density lipoprotein receptor-related protein 5/6, which is a co-receptor of the Wnt-signaling pathway, was also essential for LR asymmetric development of the AMG. These results are the first demonstration that Wnt signaling contributes to LR asymmetric development in invertebrates, as it does in vertebrates. The AMG consists of visceral muscle and an epithelial tube. Our genetic analyses revealed that Wnt signaling in the visceral muscle but not the epithelium of the midgut is required for the AMG to develop its normal laterality. Furthermore, fz2 and Wnt4 were expressed in the visceral muscles of the midgut. Consistent with these results, we observed that the LR asymmetric rearrangement of the visceral muscle cells, the first visible asymmetry of the developing AMG, did not occur in embryos lacking Wnt4 expression. Our results also suggest that canonical Wnt/β-catenin signaling, but not non-canonical Wnt signaling, is responsible for the LR asymmetric development of the AMG. Canonical Wnt/β-catenin signaling is reported to have important roles in LR asymmetric development in zebrafish. Thus, the contribution of canonical Wnt/β-catenin signaling to LR asymmetric development may be an evolutionarily conserved feature between vertebrates and invertebrates.

E and ID proteins regulate cell chirality and left–right asymmetric development in Drosophila

“…To elucidate the genetic mechanisms of LR asymmetric development in Drosophila , we carried out a genetic screen to find mutants showing LR asymmetric defects of the embryonic gut (Hozumi et al, ; Kuroda et al, ; Maeda et al, ; Nakamura et al, ; Okumura et al, ; Taniguchi et al, ). From this screen, we identified a novel allele of emc , emc tink .…”

Wnt4 is required for ostia development in the Drosophila heart

“…Drosophila Wnt4 has been shown to function through both canonical (Kuroda et al, 2012) and non-canonical Wnt signaling pathways (Cohen et al, 2002; Harris and Beckendorf, 2007; Lim et al, 2005). We genetically manipulated different Wnt signaling components to determine the pathways active in heart development.…”

The Wnt pathway limits BMP signaling outside of the germline stem cell niche in Drosophila ovaries

“…Drosophila Wnt4 is most closely related to vertebrate Wnts 9, 14 and 15 (Prud'homme et al, 2002) and has been shown to be involved in the development of dorsal epidermis, retina, heart and ovaries as well as in the left-right asymmetric morphogenesis of the midgut (Cohen et al, 2002; Hamada-Kawaguchi et al, 2014; Inaki et al, 2007; Kuroda et al, 2012; Wu et al, 2013). Wnt4 was shown to bind to both the Fz1 and Fz2 receptors (Wu and Nusse, 2002) and to signal through both the canonical and non-canonical Wnt pathways, depending on cellular contexts (Cohen et al, 2002; Hamada-Kawaguchi et al, 2014; Wu et al, 2013).…”