title: Sulfated glycosaminoglycans are necessary for Nodal signal transmission from the node to the left lateral plate in the mouse embryo.
abstract: Situs-specific organogenesis in the mouse results from leftward fluid flow in the node cavity and subsequent left-sided expression of Nodal in the lateral plate mesoderm (LPM). Nodal expression at the node is essential for the subsequent asymmetric Nodal expression in the left LPM, but the precise role of Nodal produced at the node has remained unknown. We have now investigated how the Nodal signal is transferred from the node to the LPM. Externally supplied Nodal protein failed to signal to the LPM, suggesting that the Nodal signal is transferred to the LPM via an internal route rather than an external one. Transgenic rescue experiments showed that the Nodal co-receptor Cryptic (Cfc1) is required only in the LPM, not at the node, for asymmetric Nodal expression in the LPM, indicating that the Nodal signal is not relayed indirectly between the node and LPM. Nodal interacts in vitro with sulfated glycosaminoglycans (GAGs), which are specifically localized to the basement membrane-like structure between the node and LPM in the mouse embryo. Inhibition of sulfated GAG biosynthesis prevents Nodal expression in the LPM. These data suggest that Nodal produced at the node might travel directly to the LPM via interaction with sulfated GAGs.
authors.affiliation: Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation (JST Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Oki
authors.forename: Ryuju
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okui
authors.forename: Michael M
authors.initials: MM
authors.lastname: Shen
authors.forename: Eisuke
authors.initials: E
authors.lastname: Mekada
authors.forename: Hiroki
authors.initials: H
authors.lastname: Otani
authors.forename: Yukio
authors.initials: Y
authors.lastname: Saijoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006025:Glycosaminoglycans / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D009154:Mutation / Q000235:genetics; D055457:Nodal Protein; D015398:Signal Transduction; D013455:Sulfur / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D006025:Glycosaminoglycans; D055457:Nodal Protein; C526008:Nodal protein, mouse; D016212:Transforming Growth Factor beta; D013455:Sulfur