Abstract
During vertebrate heart development, two progenitor populations, first and second heart fields (FHF, SHF), sequentially contribute to longitudinal subdivisions of the heart tube (HT), with the FHF contributing the left ventricle and part of the atria, and the SHF the rest of the heart. Here, we study the dynamics of cardiac differentiation and morphogenesis by tracking individual cells in live analysis of mouse embryos. We report that during an initial phase, FHF precursors differentiate rapidly to form a cardiac crescent, while limited morphogenesis takes place. In a second phase, no differentiation occurs while extensive morphogenesis, including splanchnic mesoderm sliding over the endoderm, results in HT formation. In a third phase, cardiac precursor differentiation resumes and contributes to SHF-derived regions and the dorsal closure of the HT. These results reveal tissue-level coordination between morphogenesis and differentiation during HT formation and provide a new framework to understand heart development.
Highlights
The heart is the first organ to form and function during embryonic development
Our results show the feasibility of live time-lapse analysis of mouse heart tube (HT) formation and reveal that splanchnic mesoderm displacement, at least in part by sliding over the endoderm, is an essential aspect of HT morphogenesis
Most of the cells that have high GFP levels at the final time point show low GFP levels at the initial time point and increase their GFP level over time (Figure 5E-G and Figure 5-source data 1). These results suggest that cardiomyocytes of the cc differentiate during 5-6 hours starting at the EHF stage, which is consistent with the onset of detectable Cardiac troponin T (cTnnT) at that stage (Figure 1B and Figure 1-figure supplement 2A, A’)
Summary
The heart is the first organ to form and function during embryonic development. At embryonic day (E) 7.5, cardiac precursors in the splanchnic mesoderm (mesoderm apposed to the endoderm) differentiate into cardiomyocytes by assembling the contractile sarcomere machinery (Tyser et al, 2016) and form a bilateral structure known as the cardiac crescent (cc) in the mouse. The right ventricle (RV), the outflow tract and most of the atria derive instead from cardiac progenitors located dorso-medially to the cc in the splanchnic mesoderm, that are progressively recruited at the poles of the HT at subsequent developmental stages (Cai et al, 2003; Kelly et al, 2001; Mjaatvedt et al, 2001; Waldo et al, 2001; Galli et al., 2008 135:1157-67) These findings led to the concept that cardiac mesodermal progenitors contain two populations of cells: the first heart field (FHF) precursors, recruited early in development to form the initial HT and mostly containing the LV primordium, and the second heart field (SHF), recruited later and elongating the HT (Buckingham et al, 2005). These results show essential properties of FHF and SHF contribution to heart development and reveal tissue-level coordination between alternating phases of differentiation and morphogenesis during HT formation
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