Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Linville A

PROVIDER: S-EPMC3045866 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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

Linville Angela A Radtke Kelly K Waxman Joshua S JS Yelon Deborah D Schilling Thomas F TF

Developmental biology 20081002 1

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 t ...[more]

PMID: 18929555

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Project description:The pharyngeal arches are a series of bulges on the lateral surface of the embryonic head. They are a defining feature of the most conserved, the phylotypic, stage of vertebrate development. In many vertebrate clades, the segmental arrangement of the pharyngeal arches is translated into the iterative anatomy of the gill arches. However, in amniotes the pharyngeal arches undergo a rearrangement during development and the segmental organisation of the pharynx is lost. This remodelling involves the expansion of the second arch which comes to overlie the more posterior arches. A transient sinus forms between the expanded second arch and the posterior arches, that is then lost, and the posterior arches are internalised. The morphogenesis of the second arch has been viewed as being central to this remodelling. Yet little is known about this process. Therefore, in this study, we have characterised the development of the second arch. We show that as the second arch expands, its posterior margin forms a leading edge and that the mesenchymal cells subjacent to this are in an elevated proliferative state. We further show that the posterior marginal epithelium is the site of expression of three key developmental signalling molecules: BMP7, FGF8 and SHH, and that their expression continues throughout the period of expansion. Using a novel approach, we have been able to simultaneously inhibit these three pathways, and we find that when this is done the second arch fails to establish its caudal projection and that there is a loss of proliferation in the posterior mesenchymal cells of the second arch. We have further used this manipulation to ask if the internalisation of the posterior arches is dependent upon the expansion of the second arch. We find that it is not-the posterior arches are still internalised when the expansion of the second arch is curtailed. We further show that while the collapse of the sinus is dependent upon thyroid hormone signalling, that this is not the case for the internalisation of the posterior pouches. Thus, the internalisation of the posterior arches is not dependent on the expansion of the second arch or on the collapse of the sinus. Finally, we show that the termination of expansion of the second arch correlates with a burst of morphogenetic cell death suggesting a mechanism for ending this. Thus, while it has long been thought that it is the morphogenesis of the second arch that drives the remodelling of the pharyngeal arches, we show that this is not the case. Rather the remodelling of the pharyngeal arches is a composite process that can split into contemporaneous but separate events: the expansion of the second arch, the internalisation of the posterior arches and the collapse of the sinus.

Dataset Information

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

Publications

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

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