| First Author | Vitobello A | Year | 2011 |
| Journal | Dev Cell | Volume | 20 |
| Issue | 4 | Pages | 469-82 |
| PubMed ID | 21497760 | Mgi Jnum | J:171613 |
| Mgi Id | MGI:4950631 | Doi | 10.1016/j.devcel.2011.03.011 |
| Citation | Vitobello A, et al. (2011) Hox and Pbx Factors Control Retinoic Acid Synthesis during Hindbrain Segmentation. Dev Cell 20(4):469-82 |
| abstractText | In vertebrate embryos, retinoic acid (RA) synthesized in the mesoderm by Raldh2 emanates to the hindbrain neuroepithelium, where it induces anteroposterior (AP)-restricted Hox expression patterns and rhombomere segmentation. However, how appropriate spatiotemporal RA activity is generated in the hindbrain is poorly understood. By analyzing Pbx1/Pbx2 and Hoxa1/Pbx1 null mice, we found that Raldh2 is itself under the transcriptional control of these factors and that the resulting RA-deficient phenotypes can be partially rescued by exogenous RA. Hoxa1-Pbx1/2-Meis2 directly binds a specific regulatory element that is required to maintain normal Raldh2 expression levels in vivo. Mesoderm-specific Xhoxa1 and Xpbx1b knockdowns in Xenopus embryos also result in Xraldh2 downregulation and hindbrain defects similar to mouse mutants, demonstrating conservation of this Hox-Pbx-dependent regulatory pathway. These findings reveal a feed-forward mechanism linking Hox-Pbx-dependent RA synthesis during early axial patterning with the establishment of spatially restricted Hox-Pbx activity in the developing hindbrain. |
