Combinatorial roles for zebrafish retinoic acid receptors in the hindbrain, limbs and pharyngeal arches

Department of Developmental and Cell Biology, Developmental Biology Center, University of California, Irvine, CA 92697, USA.
Developmental Biology (Impact Factor: 3.55). 11/2008; 325(1):60-70. DOI: 10.1016/j.ydbio.2008.09.022
Source: PubMed


Retinoic acid (RA) signaling regulates multiple aspects of vertebrate embryonic development and tissue patterning, in part through the local availability of nuclear hormone receptors called retinoic acid receptors (RARs) and retinoid receptors (RXRs). RAR/RXR heterodimers transduce the RA signal, and loss-of-function studies in mice have demonstrated requirements for distinct receptor combinations at different stages of embryogenesis. However, the tissue-specific functions of each receptor and their individual contributions to RA signaling in vivo are only partially understood. Here we use morpholino oligonucleotides to deplete the four known zebrafish RARs (raraa, rarab, rarga, and rargb). We show that while all four are required for anterior-posterior patterning of rhombomeres in the hindbrain, there are unique requirements for rarga in the cranial mesoderm for hindbrain patterning, and rarab in lateral plate mesoderm for specification of the pectoral fins. In addition, the alpha subclass (raraa, rarab) is RA inducible, and of these only raraa expression is RA-dependent, suggesting that these receptors establish a region of particularly high RA signaling through positive-feedback. These studies reveal novel tissue-specific roles for RARs in controlling the competence and sensitivity of cells to respond to RA.

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Available from: Joshua S Waxman, Sep 29, 2015
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    • "mineralization of the opercular, ceratohyal and vertebrae are reported in zebrafish (Danio rerio) mutants lacking RA degradation (Laue et al., 2008). A recent study employing systematic knockdown of RARs in zebrafish reveals the major receptors involved in pharyngeal and pectoral fin skeletogenesis (Linville et al., 2009). Except for RARs, changes of RXR expression are found in European seabass (Dicentrarchus labrax) with disturbed bone formation in the cephalic region and vertebral deformities induced by the feeding on excessive highly unsaturated fatty acid (Villeneuve et al., 2006). "
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    • "As such, vgll2a could also be acting as an effector of FGF and/ or RA signaling in the regulation of cell death. FGF and RA signaling have also been shown to regulate endodermal pouch morphogenesis (Crump et al., 2004; Kopinke et al., 2006; Linville et al., 2009). We first observe vgll2a expression in the pharyngeal endoderm in a subset of cells as they began to evaginate to form the first endodermal pouch and its expression in the pharyngeal endoderm persists throughout pouch morphogenesis. "
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