Quaking is essential for blood vessel development

Genesis. 2002 Mar;32(3):218-30. doi: 10.1002/gene.10060.

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-alpha-actin reveal that embryos homozygous for the qk(k2) 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 alpha-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Vessels / embryology*
  • Blood Vessels / physiology
  • Gene Expression Regulation, Developmental
  • Heart / embryology
  • Mice
  • Morphogenesis
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / physiology
  • Yolk Sac / blood supply
  • Yolk Sac / embryology*
  • Yolk Sac / physiology
  • Yolk Sac / ultrastructure

Substances

  • Qk protein, mouse
  • RNA-Binding Proteins