Id genes are essential for early heart formation

Thomas J. Cunningham, Michael S. Yu, Wesley L. McKeithan, Sean Spiering, Florent Carrette, Chun Teng Huang, Paul J. Bushway, Matthew Tierney, Sonia Albini, Mauro Giacca, Miguel Mano, Pier Lorenzo Puri, Alessandra Sacco, Pilar Ruiz-Lozano, Jean Francois Riou, Muriel Umbhauer, Gregg Duester, Mark Mercola, Alexandre R. Colas

Research output: Contribution to journalArticlepeer-review

Abstract

Deciphering the fundamental mechanisms controlling cardiac specification is critical for our understanding of how heart formation is initiated during embryonic development and for applying stem cell biology to regenerative medicine and disease modeling. Using systematic and unbiased functional screening approaches, we discovered that the Id family of helix-loop-helix proteins is both necessary and sufficient to direct cardiac mesoderm formation in frog embryos and human embryonic stem cells. Mechanistically, Id proteins specify cardiac cell fate by repressing two inhibitors of cardiogenic mesoderm formation-Tcf3 and Foxa2-and activating inducers Evx1, Grrp1, and Mesp1. Most importantly, CRISPR/Cas9-mediated ablation of the entire Id (Id1-4) family in mouse embryos leads to failure of anterior cardiac progenitor specification and the development of heartless embryos. Thus, Id proteins play a central and evolutionarily conserved role during heart formation and provide a novel means to efficiently produce cardiovascular progenitors for regenerative medicine and drug discovery applications.

Original languageEnglish
Pages (from-to)1325-1338
Number of pages14
JournalGenes and Development
Volume31
Issue number13
DOIs
Publication statusPublished - Jul 1 2017

Keywords

  • Cardiac mesoderm specification
  • Cardiac progenitors
  • CRISPR/Cas9-mediated quadruple knockout
  • Heartless
  • Id proteins
  • Platform for cardiac disease modeling and drug discovery

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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