Antisense oligodeoxynucleotide complementary to smooth muscle alpha-actin inhibits endothelial-mesenchymal transformation during chick cardiogenesis

Dev Dyn. 1999 Dec;216(4-5):489-98. doi: 10.1002/(SICI)1097-0177(199912)216:4/5<489::AID-DVDY17>3.0.CO;2-W.


alpha-Smooth-muscle actin (SMA) is the major isoform of adult vascular tissues. During early development, SMA is expressed in various mesodermally derived tissues in a spatiotemporally restricted manner; however, its exact role remains unknown. We examined its role in the formation of chicken atrioventricular (AV) endocardial cushion tissue. This developmental process possesses the characteristics of endothelial-mesenchymal transformation and is partly TGF beta-dependent. Immunohistochemistry showed that SMA was (1) expressed homogeneously in the newly formed appendages of transforming endothelial/mesenchymal cells, and (2) distributed in a punctate manner in the lamellipodia/filopodia of invading mesenchymal cells. Antisense oligodeoxynucleotide (ODNs) specific for SMA reduced both SMA expression and mesenchymal formation in AV endothelial cells cultured with myocardium on a collagen gel lattice. Perturbation of SMA by antisense ODN also inhibited TGF beta-inducible migratory appendage formation in a cultured AV endothelial monolayer. However, it did not inhibit cell:cell separation or cellular hypertrophy. These results suggest that the expression of SMA is necessary for migratory appendage formation during the TGF beta-dependent initial phenotypic changes that occur in endothelial-mesenchymal transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics*
  • Animals
  • Base Sequence
  • Chick Embryo
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / embryology*
  • Fluorescent Antibody Technique, Indirect
  • Heart / embryology*
  • Mesoderm / cytology
  • Mesoderm / drug effects
  • Mesoderm / physiology*
  • Oligodeoxyribonucleotides, Antisense / pharmacology*
  • Transforming Growth Factor beta / analysis


  • Actins
  • Oligodeoxyribonucleotides, Antisense
  • Transforming Growth Factor beta