XB-ART-13853Dev Genet 1998 Jan 01;233:194-202. doi: 10.1002/(SICI)1520-6408(1998)23:3<194::AID-DVG5>3.0.CO;2-0.
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Maintenance of asymmetric nodal expression in Xenopus laevis.
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.
PubMed ID: 9842714
Article link: Dev Genet
Species referenced: Xenopus laevis
Genes referenced: inhbb nodal nodal1 shh tgfb1
Article Images: [+] show captions
|Fig. 1. A: Schematic diagram of recombinant explants. Lateral plate explant from a stage 15/16 embryo is wrapped around a stage 19 notochord and allowed to heal. B: Xnr-1 expression at stage 24 assayed by in situ hybridization in isolated explants of left and right lateral plate mesoderm [from Lohr et al., 1997] and recombinant explants. Xnr-1 expression is repressed in 66% of recombinants from both right and left lateral plate. LPM, lateral plate mesoderm; N, number of explants. For left LPM recombinants, z 5 3.6, P , 0.001 vs. left LPM; for right lateral plate recombinants, z 5 3.5, P , 0.001 vs. right LPM.|
|Fig. 2. Xnr-1 expression in lateral plate (LP) grafts performed at stage 20. Embryos in A–C were fixed and assayed for Xnr-1 expression by in situ hybridization at stage 24/25. Embryos are photographed from a dorsal view with anterior at the top of the page. Photos are cropped to show relevant region only. Red arrows point to grafts, black arrows to host Xnr-1 expression, and black arrowheads to Xnr-1 expression in the grafts. A: Left LP explant is grafted onto the right side of host embryo. There is normal Xnr-1 expression in the host left lateral plate mesoderm (LPM) and no Xnr-1 expression in the left LPM grafted into the right side. B: Left LP explant grafted into the left side of the host embryo as a control for the grafting experiment in A. There is expression in both host left LPM and the graft. C: Right LP graft expresses Xnr-1 when grafted into the left LP. The host left LPM expresses Xnr-1 normally. D: Percentage of LP explants that express Xnr-1 at stage 24 by in situ hybridization when grafted into the site shown (grafts performed with donor and host at stage 20).|
|Fig. 3. A–C are dorsal views of albino Xenopus embryos at stage 24/25. Anterior is at the top of the page. A: Normal left-sided Xnr-1 expression. B: Bilateral expression of Xnr-1 in the lateral plate mesoderm and somites of an embryo injected in the right lateral plate mesoderm with 25 ng of human recombinant activin A. C: Symmetric expression of Xshh in the neural tube/floorplate of an embryo injected with 25 ng of activin into the right lateral plate at stage 20. Right lateral view of embryo (on right side of panel) indicates no ectopic Xshh expression. D: Expression of Xenopus activinbB at stage 20. (Top embryo - dorsal view with anterior towards the top of the page; bottom embryo - left lateral view). No consistent asymmetries of expression are noted.|