30 Chapter 2 mice, at the onset of gastrulation (Zhai et al., 2022). During gastrulation, cells from the blastocyst migrate to give rise to the endoderm and mesoderm. At the end of gastrulation, the three germ layers (endoderm, mesoderm and ectoderm) are specified. At the onset of mesoderm formation, the intraembryonic mesoderm subdivides into four distinct groups: the chordamesoderm, paraxial mesoderm, intermediate mesoderm and lateral plate mesoderm (Ivanovitch et al., 2021; Chan et al., 2013). Cardiopotent cells, also called cardiac progenitor cells, are derived from the lateral plate mesoderm during early gastrulation (Yamada and Takakuwa, 2012; Moretti et al., 2006; Garry and Olson, 2006). Cardiac progenitors are prepatterned within the primitive streak, with the atrial and ventricular cells arising at different anterior-posterior positions (Chan et al., 2013). Foxa2+ cardiac progenitors give rise primarily to the cardiovascular cells of the ventricles and are the first cardiogenic cells that migrate to the anterior side of the embryo (Bardot et al., 2017). These cells comprise approximately half of the cardiomyocyte population (Bardot et al., 2017). The right ventricle and outflow tract progenitors are found in anterior/distal primitive streak, where cells are exposed to a higher ratio of activin A to bone morphogenetic protein 4 (BMP4) signaling, whereas atrial progenitors are specified in the proximal primitive streak, where the activin A to BMP4 ratio is low (Ivanovitch et al., 2021). Brachyury (T) gene expression is also required for the formation of posterior mesoderm in mice and zebrafish (Schulte-Merker and Smith, 1995; Herrmann et al., 1990). Basic fibroblast growth factor (FGF) and Activin A can promote the expression of the T homolog, Xbra, in the Xenopus presumptive ectoderm (Smith et al., 1991). T-box transcription factors and T are intrinsic factors that are crucial for the initiation of mesoderm differentiation and patterning of the primitive streak and are regulated by the Wnt signaling pathway from the adjacent embryonic midline and posterior regions of the embryo, indicating the importance of Wnt signaling at this stage of development (Yamaguchi et al., 1999). Cardiac specification Several transcription factors for cardiac development have been identified (Olson, 2006). These include MESP1, which specifies the cardiac mesodermal population and is expressed in the primitive streak around CS6-7 or E6.5. In MESP1-null embryos, severe cardiac abnormalities are observed, leading to cardiac lethality by E10.5 (Saga et al., 1999). Furthermore, in a double knockout of MESP1 and its homolog MESP2, mesoderm progenitors do not contribute to heart development, indicating that MESP1/2 expression is essential for cardiac mesoderm formation (Kitajima et al., 2000). By CS8 or E7.5, specific regions of the mesoderm differentiate to form cardiovascular progenitor cells, which can be divided into cells that form the first heart field (FHF) and cells that form the second heart field (SHF) (Paige et al., 2015). When Wnt inhibitors such as dickkopf 1 (DKK1) or crescent are administered to posterior lateral plate mesoderm, heart
RkJQdWJsaXNoZXIy MTk4NDMw