title: 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.
authors.affiliation: Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Junpei
authors.initials: J
authors.lastname: Kuroda
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masashi
authors.initials: M
authors.lastname: Yoshida
authors.forename: Haruka
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Takaaki
authors.initials: T
authors.lastname: Maeda
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Naotaka
authors.initials: N
authors.lastname: Nakazawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Hatori
authors.forename: Akira
authors.initials: A
authors.lastname: Ishio
authors.forename: Ayumi
authors.initials: A
authors.lastname: Ozaki
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Shimaoka
authors.forename: Tamiko
authors.initials: T
authors.lastname: Ito
authors.forename: Hironao
authors.initials: H
authors.lastname: Iida
authors.forename: Takashi
authors.initials: T
authors.lastname: Okumura
authors.forename: Reo
authors.initials: R
authors.lastname: Maeda
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuno
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis; D004064:Digestive System / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009154:Mutation; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009928:Organ Specificity; D038081:Organogenesis; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D029721:Drosophila Proteins; D051157:Frizzled Receptors; D006023:Glycoproteins; D051153:Wnt Proteins; C454442:Wnt4 protein, Drosophila; C058784:fz protein, Drosophila; C101703:fz2 protein, Drosophila