Analysis of cardiomyocyte movement in the developing murine heart

• DOI: 10.1016/j.bbrc.2015.07.036
• Publication Date: 2015-07-10T21:58:27Z
• Authors: Hisayuki Hashimoto; Shinsuke Yuasa; Hidenori Tabata; Shugo Tohyama; Tomohisa Seki; Toru Egashira; Nozomi Hayashiji; Fumiyuki Hattori; Dai Kusumoto; Akira Kunitomi; Makoto Takei; Shin Kashimura; Gakuto Yozu; Masaya Shimojima; Chikaaki Motoda; Naoto Muraoka; Kazunori Nakajima; Asako Sakaue-Sawano; Atsushi Miyawaki; Keiichi Fukuda
• Keywords: 0303 health sciences; Myocardium; Gene Expression Regulation, Developmental; Heart; Mice, Transgenic; Cell Cycle Checkpoints; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Fetal Heart; Cell Movement; Genes, Reporter; Pregnancy; Animals; Female; Myocytes, Cardiac; Cell Proliferation; Oligonucleotide Array Sequence Analysis

The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle.