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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: 33.12). 10/2008; 134(6):921-31. DOI: 10.1016/j.cell.2008.09.002
Source: PubMed

ABSTRACT 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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    • "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 · 3.64 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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    • "Retinoids are derivatives of retinol (or vitamin A) which play an important role in the regulation and control of many biological/physiological functions such as the induction of cellular proliferation, differentiation and apoptosis [1] [2] [3] [4] [5]. These derivatives have proved to present many of the vitamin A benefits but considerable lower adverse toxicity, mainly in cases of high or long-term therapeutic doses. "
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    ABSTRACT: All-trans retinoic acid (ATRA) is a derivative of retinol (or vitamin A) presenting similar benefits but considerable lower adverse toxicity, mainly in cases of high or long-term therapeutic doses. ATRA showed to be effective in the treatment and/or chemoprevention of several epithelial and hematological malignancies and diverse dermatological and eye diseases however, its low solubility in aqueous media and photosensitivity hinder its wider usage by the conventional administration methods. Supercritical fluids technologies are being widely used to enhance the in vivo bioactivity of this type of drugs both by improving their dissolution rate (using particle size reduction processes) and/or by controlling their release into the media after incorporation into solid polymeric/inorganic matrices (using supercritical impregnation/foaming processes). In both cases the solubility of the drug in the supercritical fluid (usually scCO2) is required for process optimization purposes. Therefore, in this work the solubility of ATRA in scCO2 was measured at different isotherms (308.2, 318.2 and 328.2 K) and pressures that ranged from 10 up to 30 MPa using a static analytical method. Solubility data were correlated using three commonly used density-based models, namely the Bartle, Chrastil and Méndez-Santiago-Teja models. The solubility of ATRA in scCO2 was found to be between 1.52 × 10−6 and
    Journal of Supercritical Fluids The 01/2015; 98. DOI:10.1016/j.supflu.2014.12.027 · 2.57 Impact Factor
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