Bioelectric signaling and the control of cardiac cell identity in response to mechanical forces

Science. 2021 Oct 15;374(6565):351-354. doi: 10.1126/science.abc6229. Epub 2021 Oct 14.


Developing cardiovascular systems use mechanical forces to take shape, but how ubiquitous blood flow forces instruct local cardiac cell identity is still unclear. By manipulating mechanical forces in vivo, we show here that shear stress is necessary and sufficient to promote valvulogenesis. We found that valve formation is associated with the activation of an extracellular adenosine triphosphate (ATP)–dependent purinergic receptor pathway, specifically triggering calcium ion (Ca2+) pulses and nuclear factor of activated T cells 1 (Nfatc1) activation. Thus, mechanical forces are converted into discrete bioelectric signals by an ATP-Ca2+-Nfatc1–mechanosensitive pathway to generate positional information and control valve formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcium / metabolism
  • Calcium Signaling
  • Electrophysiological Phenomena
  • Endothelial Cells / physiology
  • Heart Valves / cytology
  • Heart Valves / growth & development*
  • Heart Valves / metabolism
  • NFATC Transcription Factors / metabolism
  • Receptors, Purinergic P2 / metabolism
  • Shear Strength*
  • Stress, Mechanical*
  • Zebrafish


  • NFATC Transcription Factors
  • Receptors, Purinergic P2
  • Adenosine Triphosphate
  • Calcium