Retinoic Acid Synthesis and Signaling during Early Organogenesis

Burnham Institute for Medical Research, Development and Aging Program, La Jolla, CA 92037, USA.
Cell (Impact Factor: 32.24). 10/2008; 134(6):921-31. DOI: 10.1016/j.cell.2008.09.002
Source: PubMed


Retinoic acid, a derivative of vitamin A, is an essential component of cell-cell signaling during vertebrate organogenesis. In early development, retinoic acid organizes the trunk by providing an instructive signal for posterior neuroectoderm and foregut endoderm and a permissive signal for trunk mesoderm differentiation. At later stages, retinoic acid contributes to the development of the eye and other organs. Recent studies suggest that retinoic acid may act primarily in a paracrine manner and provide insight into the cell-cell signaling networks that control differentiation of pluripotent cells.

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    • "There are at least three subtypes of RARs and RXRs (α,β, and γ), each with multiple isoforms (Maden et al., 1998). RA is abundant throughout the developing CNS, particularly within the spinal cord (Duester, 2008; Maden, 2007). It may also act as a chemotactic factor in the developing CNS, as it has been shown to stimulate directed neurite outgrowth in embryonic mouse dorsal root ganglia (DRG), specifically through the "
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    ABSTRACT: The molecular events underlying epimorphic regeneration of the adult urodele amphibian tail and caudal spinal cord are undetermined. Given the dynamic nature of gene expression control by retinoic acid (RA) signaling and the pleiotropic effects of microRNAs (miRNAs) on multiple mRNA targets in this complex system, we examined whether RA signaling through a specific receptor, RARβ2, alters expression of select miRNAs during spinal cord regeneration. An initial screen identified 18 highly conserved miRNAs dysregulated in regenerating tail and spinal cord tissues after inhibition of RARβ2 signaling with a selective antagonist, LE135. miRNAs let-7c, miR-1 and miR-223 were expressed within the ependymoglial cells, coincident spatially with the expression of RARβ2. Altering the expression pattern of these three miRNAs led to a significant inhibition of caudal ependymal tube outgrowth by 21 days post amputation. We demonstrated that miR-1 targets the 3' UTR of RARβ2 mRNA in vitro; and in vivo, upregulation of miR-1 led to a significant decrease in RARβ2 protein. These and previous data suggest that miR-1 and miR-133a, both members of the same miRNA gene cluster, may participate with RARβ2 in a negative feedback loop contributing to the regulation of the ependymal response after tail amputation. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Developmental Dynamics 08/2015; DOI:10.1002/dvdy.24342 · 2.38 Impact Factor
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    • "Hox genes encode a class of transcription factors that play an important role in patterning vertebrate axial development (Mallo et al., 2010; Wellik, 2009). Hox genes have been shown to respond to retinoic acid (RA), the active derivative of vitamin A, during early embryonic development (Duester, 2008; Niederreither and Dolle, 2008; Niederreither et al., 1999). Retinaldehyde dehydrogenase 2 (Raldh2) mutant embryos, which are severely impaired in their capacity to synthesize RA, develop abnormal hearts with a single ventricular chamber and highly hypoplastic sinus venosus region (Niederreither et al., 1999, 2001). "
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    ABSTRACT: Outflow tract (OFT) anomalies are among the most common congenital heart defects found at birth. The embryonic OFT grows by the progressive addition of cardiac progenitors, termed the second heart field (SHF), which originate from splanchnic pharyngeal mesoderm. Development of the SHF is controlled by multiple intercellular signals and transcription factors; however the relationship between different SHF regulators remains unclear. We have recently shown that Hoxa1 and Hoxb1 are expressed in a sub-population of the SHF contributing to the OFT. Here, we report that Hoxb1 deficiency results in a shorter OFT and ventricular septal defects (VSD). Mechanistically, we show that both Fgf/pERK and Bmp/Smad signaling, which regulate proliferation and differentiation of cardiac progenitor cells and OFT morphogenesis, are enhanced in the pharyngeal region in Hoxb1 mutants. Absence of Hoxb1 also perturbed SHF development through premature myocardial differentiation. Hence, the positioning and remodeling of the mutant OFT is disrupted. Hoxa1(-/-) embryos, in contrast, have low percentage of VSD and normal SHF development. However, compound Hoxa1(-/-);Hoxb1(+/-) embryos display OFT defects associated with premature SHF differentiation, demonstrating redundant roles of these factors during OFT development. Our findings provide new insights into the gene regulatory network controlling SHF and OFT formation. Copyright © 2015. Published by Elsevier Inc.
    Developmental Biology 08/2015; DOI:10.1016/j.ydbio.2015.08.015 · 3.55 Impact Factor
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    • "During embryonic development, retinoic acid (RA) acts as a morphogen, providing signals that instruct commitment of unspecified precursors toward separate cell fates, thereby helping to mediate tissue patterning and organogenesis (Duester, 2008; Kumar and Duester, 2011; Ross et al., 2000). As such, RA is also a potent teratogen capable of disturbing developmental processes, causing severe malformations of the fetus. "
    Dataset: 2015-Ronn
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