Endothelin-1 and Neuregulin-1 convert embryonic cardiomyocytes into cells of the conduction system in the mouse.
The cells that form the cardiac conduction system (CCS) are recruited from embryonic cardiomyocytes. Endothelin-1 (ET-1) and Neuregulin-1 (NRG-1) have been associated with this transition in the avian and murine systems, respectively. We established murine embryonic cardiomyocyte cultures induced or not with ET-1 and/or NRG-1 to compare the expression of cardiomyocyte and CCS-specific genes. Semiquantitative reverse transcription-polymerase chain reaction analysis showed that cardiomyogenesis and CCS-specific markers, such as Nkx2.5, GATA4, Irx4, Connexin 40, Connexin 45, HF-1b, and MinK, were up-regulated in the presence of either growth factor. Additionally, immunofluorescence analysis demonstrated that ET-1 or NRG-1 increased the number of cells expressing the Purkinje fiber-specific marker Connexin 40 in induced cultures but did not selectively increase their proliferation rate. Interestingly, additive effects were not observed in ET-1 and NRG-1 combination treatments. Among other possibilities, this observation suggests that these factors may interact to promote the differentiation of the murine CCS.
Patel
Rita
R
Department of Biological Sciences, Florida International University, Miami, FL 33199, USA.
Kos
Lidia
L
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D017630:Connexins / Q000096:biosynthesis / Q000235:genetics; D019332:Endothelin-1 / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006329:Heart Conduction System / Q000166:cytology / Q000502:physiology*; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D020890:Neuregulin-1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation; D000097003:Gap Junction alpha-5 Protein
D017630:Connexins; D019332:Endothelin-1; D020890:Neuregulin-1; D000097003:Gap Junction alpha-5 Protein