title: Maintenance of asymmetric nodal expression in Xenopus laevis.
abstract: Vertebrate species display consistent left-right asymmetry in the arrangement of their internal organs. This asymmetry reflects the establishment of the left-right axis and the alignment of the organs along this axis during development. Members of the TGF-beta family of molecules have been implicated in both the establishment and signaling of left-right axis information. Asymmetric expression of one member, nodal (called Xnr-1 in the frog, Xenopus laevis), is highly conserved among species. The nodal-related genes are normally expressed in the left lateral plate mesoderm prior to the development of morphologic asymmetry. Expression patterns of nodal have been correlated with heart situs in mouse, chick, and frog and our previous work has implicated the dorsal midline structures in the regulation of nodal expression and cardiac laterality. In this study, three approaches were used to address the embryologic and molecular basis of asymmetric Xnr-1 expression. First, notochord and lateral plate recombinants were performed and showed that notochord can repress Xnr-1 expression in lateral plate mesoderm explants derived from either the left or the right side. Second, lateral plate mesoderm grafts indicated that Xnr-1 expression is specified but not determined at neurula stages and can subsequently be repatterned. These experiments suggest that a repressive signal from the notochord is required for maintenance of asymmetric Xnr-1 expression and that Xnr-1 expression is regulated by signals outside of the lateral plate mesoderm. Third, candidate molecules were injected to test for their ability to alter Xnr-1 expression pattern in the lateral plate. Late injection of activin protein on the right side of the embryo induced ectopic Xnr-1 expression and randomized cardiac orientation. This suggests that activin or a related TGF-beta molecule is involved in the proximal regulation of asymmetric Xnr-1 expression.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis 55455, USA. lohrx003@tc.umn.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Lohr
authors.forename: M C
authors.initials: MC
authors.lastname: Danos
authors.forename: T W
authors.initials: TW
authors.lastname: Groth
authors.forename: H J
authors.initials: HJ
authors.lastname: Yost
mesh_terms: D028341:Activins; D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D002642:Chick Embryo; D038681:Follistatin; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000196:embryology; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D007265:Inhibins / Q000494:pharmacology; D051379:Mice; D055457:Nodal Protein; D009672:Notochord / Q000196:embryology; D011506:Proteins / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction; D015534:Trans-Activators; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics*
chemical_list: D038681:Follistatin; D006023:Glycoproteins; D053823:Hedgehog Proteins; D055457:Nodal Protein; C526008:Nodal protein, mouse; D011506:Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C512833:nodal1 protein, Xenopus; D028341:Activins; D007265:Inhibins