CASZ1 promotes vascular assembly and morphogenesis through the direct regulation of an EGFL7/RhoA-mediated pathway

Dev Cell. 2013 Apr 29;25(2):132-43. doi: 10.1016/j.devcel.2013.03.003.

Abstract

The formation of the vascular system is essential for embryonic development and homeostasis. However, transcriptional control of this process is not fully understood. Here we report an evolutionarily conserved role for the transcription factor CASZ1 (CASTOR) in blood vessel assembly and morphogenesis. In the absence of CASZ1, Xenopus embryos fail to develop a branched and lumenized vascular system, and CASZ1-depleted human endothelial cells display dramatic alterations in adhesion, morphology, and sprouting. Mechanistically, we show that CASZ1 directly regulates Epidermal Growth Factor-Like Domain 7 (Egfl7). We further demonstrate that defects of CASZ1- or EGFL7-depleted cells are in part due to diminished RhoA expression and impaired focal adhesion localization. Moreover, these abnormal endothelial cell behaviors in CASZ1-depleted cells can be rescued by restoration of Egfl7. Collectively, these studies show that CASZ1 is required to directly regulate an EGFL7/RhoA-mediated pathway to promote vertebrate vascular development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Calcium-Binding Proteins
  • Cell Adhesion
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • EGF Family of Proteins
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism*
  • Embryonic Development
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Molecular Sequence Data
  • Morphogenesis / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / growth & development
  • Xenopus laevis / metabolism*
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • CASZ1 protein, human
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • EGF Family of Proteins
  • EGFL7 protein, human
  • Egfl7 protein, Xenopus
  • Endothelial Growth Factors
  • Extracellular Matrix Proteins
  • Transcription Factors
  • Xenopus Proteins
  • rhoA GTP-Binding Protein

Associated data

  • GENBANK/JX393083