title: The left-right determinant Inversin is a component of node monocilia and other 9+0 cilia.
abstract: Inversin (Inv), a protein that contains ankyrin repeats, plays a key role in left-right determination during mammalian embryonic development, but its precise function remains unknown. Transgenic mice expressing an Inv and green fluorescent protein (GFP) fusion construct (Inv::GFP) were established to facilitate characterization of the subcellular localization of Inv. The Inv::GFP transgene rescued the laterality defects and polycystic kidney disease of Inv/Inv mice, indicating that the fusion protein is functional. In transgenic embryos, Inv::GFP protein was detected in the node monocilia. The fusion protein was also present in other 9+0 monocilia, including those of kidney epithelial cells and the pituitary gland, but it was not localized to 9+2 cilia. The N-terminal region of Inv (InvDeltaC) including the ankyrin repeats also localized to the node cilia and rescued the left-right defects of Inv/Inv mutants. Although no obvious abnormalities were detected in the node monocilia of Inv/Inv embryos, the laterality defects of such embryos were corrected by an artificial leftward flow of fluid in the node, suggesting that nodal flow is impaired by the Inv mutation. These results suggest that the Inv protein contributes to left-right determination as a component of monocilia in the node and is essential for the generation of normal nodal flow.
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.forename: Yukio
authors.initials: Y
authors.lastname: Saijoh
authors.forename: Shigenori
authors.initials: S
authors.lastname: Nonaka
authors.forename: Genta
authors.initials: G
authors.lastname: Sasaki
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Ikawa
authors.forename: Takahiko
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
mesh_terms: D000818:Animals; D017089:Ankyrin Repeat / Q000235:genetics; D002923:Cilia / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D017930:Genes, Reporter / Q000502:physiology; D007668:Kidney / Q000196:embryology; D051379:Mice / Q000196:embryology; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
chemical_list: C491947:Invs protein, mouse; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors