Induction of cardiogenesis by Hensen's node and fibroblast growth factors

Cell Tissue Res. 2002 Aug;309(2):237-49. doi: 10.1007/s00441-002-0567-2. Epub 2002 Jun 26.

Abstract

The earliest events underlying cardiac induction and morphogenesis remain largely unknown. In the present study, we show that Hensen's node, the organizer of the avian embryo, induces cardiogenesis. Specifically, following heterotopic transplantation, Hensen's node induces ectopic host tissue that expresses two early cardiac markers ( cNkx-2.5 and cNkx-2.8), as well as a ventricular marker ( VMHC1), but not an atrial marker ( AMHC1). Moreover, we examine the potential roles of candidate growth factors known to be secreted by Hensen's node. Our results show that fibroblast growth factors (FGF-2 and FGF-4) when ectopically expressed can initiate cardiac development, inducing host tissue to express the two cardiac transcription factors cNkx-2.5 and cNkx-2.8, as well as the cardiac-restricted structural gene VMHC1, but not AMHC1. In contrast to FGFs, TGFbeta family members fail to induce ectopic tissue and expression of cardiac marker genes. We also examined the effects of growth factors on the morphogenesis of the host embryo's heart. Both exogenous FGFs and TGFbeta family members perturb normal morphogenesis of the early cardiac tube and alter patterns of ventricular and atria gene expression in characteristic ways. Namely, exogenous FGFs expand areas expressing the ventricular marker VMHC1 at the expense of areas expressing the atrial marker AMHC1. Conversely, exogenous TGFbeta1 inhibits expression of VMHC1, expanding AMHC1 expression. We show here that Hensen's node and FGFs induce ectopic expression of cardiac lineage markers, and that FGF and TGFbeta family members can modulate early development of the heart. Collectively, these data suggest that the organizer plays a crucial role in cardiac induction and morphogenesis, mediated in part by endogenous members of the FGF and TGFbeta families.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / pharmacology
  • Chick Embryo
  • Embryo, Nonmammalian
  • Embryonic Induction / drug effects*
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factors / metabolism*
  • Fibroblast Growth Factors / pharmacology
  • Gene Expression Regulation, Developmental*
  • Heart / drug effects
  • Heart / embryology*
  • Humans
  • Morphogenesis
  • Myocardium / metabolism*
  • Organizers, Embryonic / metabolism*
  • Organizers, Embryonic / transplantation
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / pharmacology
  • Quail
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology
  • Transplantation, Heterotopic

Substances

  • BMP2 protein, human
  • Biomarkers
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • FGF4 protein, human
  • Fibroblast Growth Factor 4
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factors