The Role of Quaking in Mammalian Embryonic Development

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 693)


Functional studies of the mouse quaking gene (Qk) have focused on its role in the postnatal central nervous system during myelination. However, the death of the majority of homozygous mouse quaking alleles revealed that quaking has a critical role in embryonic development prior to the start of myelination. Surprisingly, the lethal alleles revealed that quaking has a function in embryonic blood vessel formation and remodeling. Further studies of the extraembryonic yolk sac showed that Qk regulates visceral endoderm differentiated function at the cellular level, including the local synthesis of retinoic acid (RA), which then exerts paracrine control of endothelial cells within adjacent mesoderm. Endoderm-derived RA regulates proliferation of endothelial cells and extracellular matrix (ECM) production, which in a reciprocal manner, modulates visceral endoderm survival and function. Although exogenous RA can rescue endothelial cell growth control and ECM production in mutants carrying a lethal mutation, which lack functional Qk, neither visceral endoderm function nor vascular remodeling is restored. Thus, Qk also regulates cell autonomous functions of visceral endoderm that are critical for vascular remodeling. Interestingly, quaking is highly expressed during normal cardiac development, particularly in the outflow tract, suggesting potentially unique functions in the developing heart. Together, the work on Qk in mammalian embryos reveals an essential, yet under appreciated, role in cardiovascular development. This suggests that certain functions may remain conserved in the early embryo throughout the evolution of nonvertebrate and vertebrate organisms and that additional roles for quaking remain to be discovered.


Retinoic Acid Vascular Remodel Mural Cell Visceral Endoderm Star Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Departments of Molecular and Human Genetics and Molecular Physiology and BiophysicsBaylor College of MedicineUSA

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