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XB-ART-43130
Dev Cell. April 19, 2011; 20 (4): 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
.
Abstract 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 Article link: Dev Cell.Grant support:
1R01HD061403-01 NICHD NIH HHS , 2R01HD043997-06 NICHD NIH HHS , 3R21DE018031-02S1 NIDCR NIH HHS Genes referenced: aldh1a2 hoxa1 meis2 pbx1 pbx2 Antibodies referenced: Article Images: [+] show captions
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