Involvement of neurons and retinoic acid in lymphatic development: new insights in increased nuchal translucency. (22nd August 2014)

• Record Type: Journal Article
• Authors: Burger, Nicole B.; Stuurman, Kyra E.; Kok, Evelien; Konijn, Tanja; Schooneman, Dennis; Niederreither, Karen; Coles, Mark; Agace, William W.; Christoffels, Vincent M.; Mebius, Reina E.; van de Pavert, Serge A.; Bekker, Mireille N.
• Is Part Of: Prenatal diagnosis. Volume 34:Number 13(2014:Dec.)
• Page Start: 1312
• Page End: 1319
• Publication Date: 2014-08-22
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.4473
• Languages: English
• ISSNs: 0197-3851

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <sec id="pd4473-sec-0001" sec-type="section"> <title>Objective</title> <p>Increased nuchal translucency originates from disturbed lymphatic development. Abnormal neural crest cell (NCC) migration may be involved in lymphatic development. Because both neuronal and lymphatic development share retinoic acid (RA) as a common factor, this study investigated the involvement of NCCs and RA in specific steps in lymphatic endothelial cell (LEC) differentiation and nuchal edema, which is the morphological equivalent of increased nuchal translucency.</p> </sec> <sec id="pd4473-sec-0002" sec-type="section"> <title>Methods</title> <p>Mouse embryos in which all NCCs were fluorescently labeled (<italic>Wnt1‐Cre;Rosa26<sup>eYfp</sup></italic>), reporter embryos for <italic>in vivo</italic> RA activity (DR5‐luciferase) and embryos with absent (<italic>Raldh2<sup>−/−</sup></italic>) or <italic>in utero</italic> inhibition of RA signaling (BMS493) were investigated. Immunofluorescence using markers for blood vessels, lymphatic endothelium and neurons was applied<italic>.</italic> Flow cytometry was performed to measure specific LEC populations.</p> </sec> <sec id="pd4473-sec-0003" sec-type="section"> <title>Results</title> <p>Cranial nerves were consistently close to the jugular lymph sac (JLS), in which NCCs were identified. In the absence of RA synthesis, enlarged JLS and nuchal edema were observed. Inhibiting RA signaling <italic>in utero</italic> resulted in a significantly higher amount of precursor‐LECs at the expense of mature LECs and caused nuchal edema.</p> </sec> <sec id="pd4473-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Neural crest cells are involved in lymphatic development. RA is required for differentiation into mature LECs. Blocking RA signaling in mouse embryos results in abnormal lymphatic development and nuchal edema. © 2014 John Wiley & Sons, Ltd.</p> </sec> </abstract>