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Dev Cell April 19, 2011; 20 (4): 469-82.
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Hox and Pbx factors control retinoic acid synthesis during hindbrain segmentation.

Vitobello A , Ferretti E , Lampe X , Vilain N , Ducret S , Ori M , Spetz JF , Selleri L , Rijli FM .

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.

PubMed ID: 21497760
PMC ID: PMC3677862
Article link: Dev Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: aldh1a2 egr2 gal.2 hoxa1 meis2 pbx1 pbx2
Morpholinos: hoxa1 MO1 hoxa1 MO2 pbx1 MO1

Article Images: [+] show captions
References [+] :
Barrow, Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse. 2000, Pubmed