Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis

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.

Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development

“…Over a well-defined developmental window, multi-potent, latedifferentiating progenitors of the SHF migrate into the poles of the heart tube to extensively remodel and add structure to the heart (Cai et al, 2003;van den Berg et al, 2009;Hutson et al, 2010;Kelly, 2012). It remains under debate, however, whether the FHF and SHF represent truly distinct populations with unique molecular signatures, or whether they exist as one population with a gradient in timing for deployment to the heart (Abu-Issa et al, 2004;Moorman et al, 2007;Ivanovitch et al, 2017).…”

Embryonic organoids recapitulate early heart organogenesis

“…4A). These further developed into denser crescent-like structures with beating areas, leading to beating epithelial protrusions on the anterior portion of the gastruloids at around 168 h. Similar to mouse embryos (Ivanovitch et al, 2017;Le Garrec et al;Tyser et al, 2016), these phenotypes could be observed in gastruloids within 24 h, and could be aligned to progressive morphological stages of embryonic cardiac development between E7.5 and E8.5 (Fig. 4B).…”

“…4D,E, Supplemental Movie 5). This is reminiscent of the spatial arrangement of anterior structures in the developing embryo (Ivanovitch et al, 2017).…”

“…The presence of a crescent-like structure and its evolution to a coherent beating group of cells led us to test whether this was accompanied by an association between the crescent and anterior endoderm, as is the case in the embryo (Ivanovitch et al, 2017;Lough and Sugi, 2000). Bulk transcriptomics analysis of late gastruloids revealed gene expression patterns (Sox17, Shh, CDX2) that suggested the presence of a primitive gut-tube-like tissue (Beccari et al, 2018).…”

Understanding the Mechanobiology of Early Mammalian Development through Bioengineered Models

“…Regardless, while both the mouse and human micropattern platforms described above are perfect examples of the value of engineering approaches to development, in vivo cell fate specification and morphogenesis are heavily dependent on the 3D context of the developing embryo. In vivo development involves folding of tissues (e.g., neural, gut, or heart tube development) (Ivanovitch et al, 2017;Nikolopoulou et al, 2017;Spence et al, 2011), tissue migration and intercalation (e.g., gastrulation, notochord morphogenesis; Balmer et al, 2016;Rivera-Pé rez and Hadjantonakis, 2014;Viotti et al, 2014), and compartmentalization of soluble signals and their receptors (Zhang et al, 2018b). Understandably, these are features that cannot all be recapitulated by monolayer systems.…”