Quaking is essential for blood vessel development

Authors

  • Janice K. Noveroske,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Lihua Lai,

    1. Department of Pediatrics and Molecular and Cellular Biology, Centers for Cell and Gene Therapy and Children's Nutrition Research, Baylor College of Medicine, Houston, Texas
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  • Vinciane Gaussin,

    1. Cardiovascular Research Institute, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, and Hackensack University Medical Center, Hackensack, New Jersey
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  • Jennifer L. Northrop,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Hisashi Nakamura,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Karen K. Hirschi,

    1. Department of Pediatrics and Molecular and Cellular Biology, Centers for Cell and Gene Therapy and Children's Nutrition Research, Baylor College of Medicine, Houston, Texas
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  • Monica J. Justice

    Corresponding author
    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    • Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030
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Abstract

For nearly 40 years functional studies of the mouse quaking gene (qkI) have focused on its role in the postnatal central nervous system during myelination. However, the homozygous lethality of a number of ENU-induced alleles reveals that quaking has a critical role in embryonic development prior to the start of myelination. In this article, we show that quaking has a previously unsuspected and essential role in blood vessel development. Interestingly, we found that quaking, a nonsecreted protein, is expressed in the yolk sac endoderm, adjacent to the mesodermal site of developing blood islands, where the differentiation of blood and endothelial cells first occurs. Antibodies against PE-CAM-1, TIE-2 and SM-α-actin reveal that embryos homozygous for the qkk2 allele have defective yolk sac vascular remodeling and abnormal vessels in the embryo proper at midgestation, coinciding with the timing of embryonic death. However, these mutants exhibit normal expression of Nkx2.5 and α-sarcomeric actin, indicating that cardiac muscle differentiation was normal. Further, they had normal embryonic heart rates in culture, suggesting that cardiac function was not compromised at this stage of embryonic development. Together, these results suggest that quaking plays an essential role in vascular development and that the blood vessel defects are the cause of embryonic death. genesis 32:218–230, 2002. © 2002 Wiley-Liss, Inc.

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