Cellular Mechanism of Mouse Atrial Development

During the development of mammalian heart, the left and right atria play an important role in cardiovascular circulation. The embryonic atrium is mainly formed by the differentiation of progenitor cells and the proliferation of cardiomyocytes, while the postnatal atrium is primarily shaped by the increase in the volume of cardiomyocytes. Cell proliferation and differentiation of atrial development is the basis for its functions such as “blood reservoir” and “supplementary pump”. Deep understanding the cellular mechanism of atrial development is imperative to explore the causes of common congenital arrhythmia heart diseases such as atrial fibrillation. We used genetically engineered mouse reproduction knowledge, lineage tracing method based on CreloxP system, molecular biology and immunofluorescence technology to track the cardiomyocyte lineage of Nppa-GFP mouse line with stereo fluorescence microscope and ultra-high-speed confocal microscope. Besides the atrium of Nppa-CreER; Rosa26 tdTomato mouse was examined during embryonic (E10.5 - E18.5) and postnatal (P0, P3, P5, P7, P14, P28, P8w) stage. Immunofluorescence results revealed that Nppa-positive cells labeled TNNI3-positive cardiomyocytes and protruded into the atrial cavity at the beginning of E11.5 - E12.0 and during subsequent development to form Nppa-positive myocardial trabeculae. Thick comb-shaped myocardium was observed after birth, and we suspect that this was particularly important for the normal contractile activity and pumping function of the atrium. Additionally, non-single origin of Nppa-positive trabecular myocardiocytes were revealed through Tamoxifen-induced lineage tracing experiment. Our findings reveal proliferation dynamics and non-comprehensive fate decisions of cardiomyocytes that produce the distinct architecture of the atrium chamber.