A single-cell transcriptional roadmap for cardiopharyngeal fate diversification

Nat Cell Biol. 2019 Jun;21(6):674-686. doi: 10.1038/s41556-019-0336-z. Epub 2019 Jun 3.

Abstract

In vertebrates, multipotent progenitors located in the pharyngeal mesoderm form cardiomyocytes and branchiomeric head muscles, but the dynamic gene expression programmes and mechanisms underlying cardiopharyngeal multipotency and heart versus head muscle fate choices remain elusive. Here, we used single-cell genomics in the simple chordate model Ciona to reconstruct developmental trajectories forming first and second heart lineages and pharyngeal muscle precursors and characterize the molecular underpinnings of cardiopharyngeal fate choices. We show that FGF-MAPK signalling maintains multipotency and promotes the pharyngeal muscle fate, whereas signal termination permits the deployment of a pan-cardiac programme, shared by the first and second heart lineages, to define heart identity. In the second heart lineage, a Tbx1/10-Dach pathway actively suppresses the first heart lineage programme, conditioning later cell diversity in the beating heart. Finally, cross-species comparisons between Ciona and the mouse evoke the deep evolutionary origins of cardiopharyngeal networks in chordates.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Ciona intestinalis / genetics*
  • Ciona intestinalis / growth & development
  • Fibroblast Growth Factors / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Genomics
  • Heart / growth & development*
  • Mesoderm / growth & development
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / metabolism
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Pharyngeal Muscles / growth & development*
  • T-Box Domain Proteins / genetics*
  • Transcription Factors / genetics

Substances

  • T-Box Domain Proteins
  • Transcription Factors
  • Fibroblast Growth Factors
  • Mitogen-Activated Protein Kinase Kinases