The RXRalpha gene functions in a non-cell-autonomous manner during mouse cardiac morphogenesis.
Germline mutation in mice of the retinoic acid receptor gene RXRalpha results in a proliferative failure of cardiomyocytes, which leads to an underdeveloped ventricular chamber and midgestation lethality. Mutation of the cell cycle regulator N-myc gene also leads to an apparently identical phenotype. In this study, we demonstrate by chimera analysis that the cardiomyocyte phenotype in RXRalpha-/- embryos is a non-cell-autonomous phenotype. In chimeric embryos made with embryonic stem cells lacking RXRalpha, cardiomyocytes deficient in RXRalpha develop normally and contribute to the ventricular chamber wall in a normal manner. Because the ventricular hypoplastic phenotype reemerges in highly chimeric embryos, we conclude that RXRalpha functions in a non-myocyte lineage of the heart to induce cardiomyocyte proliferation and accumulation, in a manner that is quantitatively sensitive. We further show that RXRalpha is not epistatic to N-myc, and that RXRalpha and N-myc regulate convergent obligate pathways of cardiomyocyte maturation.
Tran
C M
CM
Institute for Genetic Medicine, University of Southern California School of Medicine, Los Angeles, CA 90033, USA.
Sucov
H M
HM
D000818:Animals; D002455:Cell Division; D002678:Chimera; D003433:Crosses, Genetic; D005796:Genes / Q000502:physiology; D006352:Heart Ventricles / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009024:Morphogenesis; D009206:Myocardium / Q000166:cytology; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000502:physiology; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors