High-affinity folate receptor in cardiac neural crest migration: A gene knockdown model using siRNA

Authors

  • Thomas H. Rosenquist,

    1. Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska
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  • Tammy Chaudoin,

    1. Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska
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  • Richard H. Finnell,

    1. Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas
    2. The Texas A&M Institute for Genomic Medicine, Department of Genetics, Cell Biology and Anatomy, Houston, Texas
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  • Gregory D. Bennett

    Corresponding author
    1. Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska
    • Department Genetic Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha NE 68198-5805
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Abstract

Folate supplementation reduces the incidence of congenital heart defects, but the nature of this protective mechanism remains unclear. Immunolabeling demonstrated that the neural tube and neural crest (NC) cells were rich in the high-affinity folate receptor FOLR1and during the early stages of development FOLR1 was found principally in these cells. Suppression of Folr1 expression in the nascent cardiac NC by site-directed short-interfering RNA (siRNA) altered cardiac NC cell mitosis and subsequent migration patterns leading to abnormal development of the pharyngeal arch arteries (PAA) and outflow tract. qPCR analysis demonstrated that the siRNA treatment significantly reduced Folr1 24 hr after treatment. These treatments also significantly reduced mitosis in the neural tube, but adjacent, nontreated areas were unaffected. In summary, a brief reduction in the expression of Folr1 during a critical stage of NC development had long-term consequences for the development of the PAA and outflow tract. Developmental Dynamics 239:1136–1144, 2010. © 2010 Wiley-Liss, Inc.

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