FGF signaling enforces cardiac chamber identity in the developing ventricle

Development. 2017 Apr 1;144(7):1328-1338. doi: 10.1242/dev.143719. Epub 2017 Feb 23.

Abstract

Atrial and ventricular cardiac chambers behave as distinct subunits with unique morphological, electrophysiological and contractile properties. Despite the importance of chamber-specific features, chamber fate assignments remain relatively plastic, even after differentiation is underway. In zebrafish, Nkx transcription factors are essential for the maintenance of ventricular characteristics, but the signaling pathways that operate upstream of Nkx factors in this context are not well understood. Here, we show that FGF signaling plays an essential part in enforcing ventricular identity. Loss of FGF signaling results in a gradual accumulation of atrial cells, a corresponding loss of ventricular cells, and the appearance of ectopic atrial gene expression within the ventricle. These phenotypes reflect important roles for FGF signaling in promoting ventricular traits, both in early-differentiating cells that form the initial ventricle and in late-differentiating cells that append to its arterial pole. Moreover, we find that FGF signaling functions upstream of Nkx genes to inhibit ectopic atrial gene expression. Together, our data suggest a model in which sustained FGF signaling acts to suppress cardiomyocyte plasticity and to preserve the integrity of the ventricular chamber.

Keywords: Amhc; Atrium; Nkx2.5; Ventricle; Vmhc; Zebrafish.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Fibroblast Growth Factors / metabolism*
  • Gene Expression Regulation, Developmental
  • Heart Atria / cytology
  • Heart Ventricles / cytology
  • Heart Ventricles / embryology*
  • Heart Ventricles / metabolism*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Organogenesis* / genetics
  • Signal Transduction* / genetics
  • Time Factors
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish / metabolism*
  • Zebrafish Proteins / metabolism

Substances

  • Zebrafish Proteins
  • Fibroblast Growth Factors