Cardiotrophin-1 displays early expression in the murine heart tube and promotes cardiac myocyte survival

Development. 1996 Feb;122(2):419-28. doi: 10.1242/dev.122.2.419.


We have recently isolated a novel cytokine, cardiotrophin-1 (CT-1), from an in vitro embryonic stem cell system of cardiogenesis that can activate embryonic markers in neonatal rat cardiac myocytes. CT-1 is a new member of the interleukin 6 (IL-6)/leukemia inhibitory factor (LIF) cytokines, which activate downstream signals via gp130-dependent pathways. To define the developmental pattern of expression of CT-1 during murine embryogenesis, we have developed antibodies directed against a CT-1 fusion protein. As assessed by immunolocalization, CT-1 is predominantly expressed in the early mouse embryonic heart tube (E8.5-10.5). In the heart, CT-1 is primarily expressed in myocardial cells, and not in endocardial cushion or outflow tract tissues. After E12.5, CT-1 expression is found in other tissues, including skeletal, liver and dorsal root ganglia. Given the effects of a related family member (ciliary neurotrophic factor, CNTF) on neuronal cell survival, we studied the ability of CT-1 to promote cardiac myocyte survival and proliferation in vitro. Both CT-1 and LIF, which share the same receptors, dramatically promote neonatal cardiac myocyte survival, while IL-6 and CNTF are without effect. A cell proliferation assay documents that CT-1 provokes an approximate 2-fold increase in embryonic cardiac myocyte proliferation. Thus, CT-1 may play an autocrine role during cardiac chamber growth and morphogenesis by promoting the survival and proliferation of immature myocytes, most likely via gp130-dependent signaling pathways.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Base Sequence
  • Cell Division
  • Cell Survival
  • Cells, Cultured
  • Cytokines / analysis
  • Cytokines / biosynthesis*
  • DNA Primers
  • Embryonic and Fetal Development*
  • Ganglia, Spinal / embryology
  • Ganglia, Spinal / metabolism
  • Gene Expression Regulation*
  • Gestational Age
  • Heart / embryology*
  • Immunohistochemistry
  • Liver / embryology
  • Liver / metabolism
  • Mice
  • Molecular Sequence Data
  • Muscle, Skeletal / embryology
  • Muscle, Skeletal / metabolism
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Organ Specificity
  • Polymerase Chain Reaction
  • Rats
  • Stem Cells / physiology


  • Cytokines
  • DNA Primers
  • cardiotrophin 1