Heart of Glass Regulates the Concentric Growth of the Heart in Zebrafish

Curr Biol. 2003 Dec 16;13(24):2138-47. doi: 10.1016/j.cub.2003.11.055.

Abstract

Background: Patterned growth of vertebrate organs is essential for normal physiological function, but the underlying pathways that govern organotypic growth are not clearly understood. Heart function is critically dependent upon the concentric thickening of the ventricular wall generated by the addition of cells to the myocardium along the axis from the endocardium (inside) to the outside of the chamber. In heart of glass mutant embryos, the number of cells in the myocardium is normal, but they are not added in the concentric direction. As a consequence, the chambers are huge and dysfunctional, and the myocardium remains a single layer.

Results: To begin to define the factors controlling the concentric growth of cells in the myocardium, we used positional cloning to identify the heart of glass (heg) gene. heg encodes a protein of previously undescribed function, expressed in the endocardial layer of the heart. By alternative splicing, three distinct isoforms are generated, one of which is predicted to be transmembrane and two other secreted. By selective morpholino perturbation, we demonstrate that the transmembrane form is critical for the normal pattern of growth.

Conclusions: heart of glass encodes a previously uncharacterized endocardial signal that is vital for patterning concentric growth of the heart. Growth of the heart requires addition of myocardial cells along the endocardial-to-myocardial axis. This axis of patterning is driven by heg, a novel transmembrane protein expressed in the endocardium.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromatography
  • DNA Primers
  • Gene Expression Regulation, Developmental*
  • Gene Transfer Techniques
  • Heart / embryology*
  • Histological Techniques
  • Immunohistochemistry
  • In Situ Hybridization
  • Membrane Glycoproteins / genetics*
  • Microscopy, Electron
  • Molecular Sequence Data
  • Myocardium / cytology*
  • Myocardium / ultrastructure
  • Organogenesis / genetics
  • Protein Conformation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins / genetics*

Substances

  • DNA Primers
  • Membrane Glycoproteins
  • Zebrafish Proteins
  • heg1 protein, zebrafish