Evolutionary conservation of mechanisms upstream of asymmetric Nodal expression: reconciling chick and Xenopus.
Recent experiments have suggested a pathway of genes that regulate left-right asymmetry in vertebrate embryogenesis. The most downstream member of this cascade is nodal (XNR-1 in frogs), which is expressed in the left-side lateral mesoderm. Previous work in the chick [Levin, 1998] suggests that an inductive interaction by Shh (Sonic hedgehog) present at the midline was needed for the left-sided expression of nodal, which by default would not be expressed. Interestingly, it has been reported [Lohr et al., 1997] that in Xenopus, right-side mesoderm that is explanted at st. 15 and allowed to develop in culture, goes on to express nodal, suggesting that lateral mesoderm expresses this gene by default and that a repression of nodal by the midline is needed to achieve asymmetry. Such a contradiction raises interesting questions about the degree of conservation of the mechanisms upstream of nodal asymmetry and, in general, about the differences in the LR pathway among species. Thus we examined this issue directly. We show that in the chick, as in the frog, explanted mesoderm from both sides does, indeed, go on to express nodal, including both the medial and lateral expression domains. Ectopic nodal expression in the medial domain on the right side is not sufficient to induce an ectopic lateral domain. We also show that explanted lateral tissue regenerates node/notochord structures exhibiting Shh expression. Furthermore, we show that Xenopus explants done at st. 15 also regenerate notochord by the stage at which XNR-1 would be expressed. Thus explants are not isolated from the influence of the midline. In contrast to the midline repressor model previously suggested [Lohr et al., 1997] to explain the presence of nodal expression in explants, we propose that the expression is due to induction by signals secreted by regenerating node and notochord tissue (Shh in the chick). Thus our results are consistent with Shh being necessary for nodal induction in both species, and we provide an explanation for both sets of data in terms of a single conserved mechanism upstream of nodal expression.
Levin
M
M
Cell Biology Dept., Harvard Medical School, Boston, MA 02115, USA. mlevin@fas.harvard.edu
Mercola
M
M
D000818:Animals; D005075:Biological Evolution; D019521:Body Patterning / Q000235:genetics; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D055457:Nodal Protein; D009672:Notochord / Q000196:embryology / Q000502:physiology; D011506:Proteins / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D013045:Species Specificity; D015534:Trans-Activators; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014981:Xenopus / Q000196:embryology* / Q000235:genetics*
D053823:Hedgehog Proteins; D055457:Nodal Protein; D011506:Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta