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.
journal_name
Dev Celljournal_title
Developmental cellauthors
Vitobello A,Ferretti E,Lampe X,Vilain N,Ducret S,Ori M,Spetz JF,Selleri L,Rijli FMdoi
10.1016/j.devcel.2011.03.011subject
Has Abstractpub_date
2011-04-19 00:00:00pages
469-82issue
4eissn
1534-5807issn
1878-1551pii
S1534-5807(11)00115-8journal_volume
20pub_type
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