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: 3.64). 11/2008; 325(1):60-70. DOI: 10.1016/j.ydbio.2008.09.022
Source: PubMed

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.

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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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    ABSTRACT: Invertebrate and vertebrate vestigial (vg) and vestigial-like (VGLL) genes are involved in embryonic patterning and cell fate determination. These genes encode cofactors that interact with members of the Scalloped/TEAD family of transcription factors and modulate their activity. We have previously shown that, in mice, Vgll2 is differentially expressed in the developing facial prominences. In this study, we show that the zebrafish ortholog vgll2a is expressed in the pharyngeal endoderm and ectoderm surrounding the neural crest derived mesenchyme of the pharyngeal arches. Moreover, both the FGF and retinoic acid (RA) signaling pathways, which are critical components of the hierarchy controlling craniofacial patterning, regulate this domain of vgll2a expression. Consistent with these observations, vgll2a is required within the pharyngeal endoderm for NCC survival and pharyngeal cartilage development. Specifically, knockdown of Vgll2a in zebrafish embryos using Morpholino injection results in increased cell death within the pharyngeal arches, aberrant endodermal pouch morphogenesis, and hypoplastic cranial cartilages. Overall, our data reveal a novel non-cell autonomous role for Vgll2a in development of the NCC-derived vertebrate craniofacial skeleton.
    Developmental Biology 09/2011; 357(1):269-81. DOI:10.1016/j.ydbio.2011.06.034 · 3.64 Impact Factor
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    • "Regarding pectoral fin development, knockdown of RARb resulted in a loss of pectoral fin cartilage. In contrast, knockdown of RARaa, RARga or RARgb did not affect fin cartilage (Linville et al., 2009). Collectively, these results suggest that rarb is essential for the development of pectoral fin cartilage. "
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    ABSTRACT: Vitamin A (VA) is an essential nutrient in fish. VA is involved in a large spectrum of biological processes. One of the most important functions of VA is to control embryonic development in animals. In mammals, organogenesis is completed during embryogenesis. In contrast, most marine fish larvae are in a comparatively immature state at hatching and undergo organogenesis during the exogenous feeding stage. This developmental feature of marine fish larvae requires appropriate control of the nutritional composition of the diet to support normal skeleton development. Nutrient deficiency or imbalance results in skeletal deformities that are often recognized in hatchery-reared fish. However, the etiology and precise mechanism of such skeletal deformities are unknown, which makes it difficult to achieve an effective prevention protocol in hatcheries. Skeletal deformities induced by excess VA are a popular model for studying the development of skeletons in fish larvae. Several studies suggest the importance of retinoic acid receptor (RAR) and retinoid X receptor (RXR) pathways in skeletogenesis in fish. This paper reviews the current understanding of VA-induced skeletal deformities and recent progress in this area and proposes future perspectives for model studies.
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