Tsukui et al., 1999 - Multiple left-right asymmetry defects in Shh(-/-) mutant mice unveil a convergence of the shh and retinoic acid pathways in the control of Lefty-1. Proceedings of the National Academy of Sciences of the United States of America   96(20):11376-11381 Full text @ Proc. Natl. Acad. Sci. USA

Fig. 3 RA alters Lefty and Pitx2 gene expression. (A-C, ventral views) Treatment of mouse embryos for 4-6 hr with the retinoic antagonist AGN 193109 (10-7 M) down-regulates Pitx2 expression on the left LPM (arrow in A; wild type in B). Treatment of mouse embryos with RA (10-7 M) for 4-6 hr at the head fold stage induces Pitx2 expression on the right LPM (red arrow in C). (D-M) Treatment of zebrafish (D-F, dorsal views), Xenopus (G-J, lateral views), and chicken (K-M, dorsal views) with RA antagonist, or RA, down-regulates or induces Pitx2 expression, respectively (black arrows indicate normal expression in the left LPM and red arrows indicate ectopic expression in the right LPM). (N-P) Chicken embryos that were allowed to develop until stage 12 after treatment with RA antagonist (N) or RA (P) display a randomization of heart looping. Here we show hearts looping to the left (compare with the wild-type heart that loops to the right in O). (Q-V, ventral views) Treatment of mouse embryos at the head fold stage with RA antagonist (10-7 M) for 6 hr results in down-regulation of Lefty-1 and Lefty-2 genes in both the midline and LPM (arrows in Q; normal expression in R). On the other hand, similar treatment with RA induces ectopic expression of Lefty genes (red arrow in S). In the chicken embryo, when a bead soaked in RA antagonist is implanted on the left side of the node at stage 6, Lefty-1 expression is abolished (T; normal expression in U). On the contrary, RA beads implanted on the right side of the node of stage 6 chicken embryos induce Lefty-1 expression on the posterior right LPM (red arrow in V; black arrow indicates normal expression on the posterior left LPM). In the dorsal views (D-F and K-M), the left side of the embryo corresponds to the reader's left). WT, wild type.

Acknowledgments:
ZFIN wishes to thank the journal Proceedings of the National Academy of Sciences of the United States of America for permission to reproduce figures from this article. Please note that this material may be protected by copyright. Full text @ Proc. Natl. Acad. Sci. USA