Epicardial Induction of Fetal Cardiomyocyte Proliferation via a Retinoic Acid-Inducible Trophic Factor

We have investigated the underlying mechanistic basis of this phenotype

Tim H.-P. Chen; Tsai-Ching Chang; Ji-One Kang; Bibha Choudhary; Takako Makita; Chanh M. Tran; John B.E. Burch; Hoda Eid; Henry M. Sucov

2002

Scholarcy highlights

  • Mouse embryos lacking the retinoic acid receptor RXRα properly undergo the early steps of heart development, but fail to initiate a proliferative expansion of cardiomyocytes that normally results in the formation of the compact zone of the ventricular chamber wall
  • We find that interference with retinoic acid receptor function in the epicardium of transgenic embryos recapitulates the hypoplastic phenotype of RXRα deficient embryos
  • We further show that wild type primary epicardial cells, and an established epicardial cell line, secrete trophic protein factors into conditioned media that stimulate thymidine incorporation in primary fetal cardiomyocytes, and thymidine incorporation, cell cycle progression, and induction of cyclin D1 and E activity in NIH3T3 cells
  • We propose that the fetal epicardium, in response to retinoic acid and in a manner requiring the activity of RXRα, secretes trophic factors which drive fetal cardiomyocyte proliferation and promote ventricular chamber morphogenesis

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