Fate Map Comparisons Indicate that RA Signaling Limits the Number of Atrial and Ventricular Cardiomyocytes through Independent Mechanisms
(A) Schematic of an embryo at 40% epiboly, lateral view, dorsal to the right. Blue grid indicates the coordinates of the marginal region of the embryo represented in the fate maps. The vertical axis indicates the cell tier (latitude), the distance in cell diameters from the embryonic margin. The horizontal axis indicates the angular distance (longitude) from the dorsal midline (0°:) in a clockwise or counterclockwise direction along the embryonic circumference.
(B and C) Cardiomyocyte progenitor fate maps from wild-type embryos (Keegan et al., 2004) (B), and BMS-treated embryos (Keegan et al., 2005) (C). The portion of the embryonic margin containing cardiomyocyte progenitors overlaps with the expression of raldh2 in lateral and ventral mesendoderm at 40% epiboly (Begemann et al., 2001; Grandel et al., 2002; Keegan et al., 2004). Each circle represents the location of labeled cells in an individual experimental embryo. Green and red circles indicate that labeled cells gave rise to atrial or ventricular cardiomyocyte progeny, respectively. Brown circles indicate experiments in which labeled cells did not give rise to cardiomyocyte progeny. Green and red backgrounds indicate territories where atrial and ventricular progenitors, respectively, are found in both the wild-type and BMS-treated fate maps (schematized in Figures 1L and 1M). Striped background indicates territories containing atrial and ventricular progenitors. Atrial progenitors arose from similar territories in wild-type and BMS-treated embryos: in wild-type embryos, blastomeres giving rise to atrial progeny were found between 90°:-135°: in tier 2, between 100°:-140°: in tier 3, and between 105°:-110°: in tier 4, while in BMS-treated embryos, they were found between 100°:-135°: in tier 2, between 100°:-160°: in tier 3, and between 115°:-120°: in tier 4 (see also Supplemental Table 3). However, our data suggested that there may be a slightly broader distribution of ventricular progenitors in BMS-treated embryos than in wild-type embryos: in wild-type embryos, blastomeres giving rise to ventricular progeny were found between 60°:-125°: in tier 1, between 60°:-120°: in tier 2, and between 90°:-95°: in tier 3, whereas in BMS-treated embryos, they were found between 50°:-150°: in tier 1, between 60°:-125°: in tier 2, and between 65°:-115°: in tier 3 (see also Supplemental Table 3). Even considering this modest expansion, the territories containing atrial and ventricular progenitors appeared comparable in wild-type and BMS-treated embryos at 40% epiboly. Additionally, reduction of RA signaling does not disrupt the frequency of encountering atrial progenitors within the green territories (see Figure 1N). However, reduction of RA signaling does cause a marked increase in the frequency of encountering ventricular progenitors within red territories (see Figure 1N).
Wild-type fate map data were presented previously in a different format (Keegan et al., 2004). A portion of the BMS189453 fate map data was presented previously in a different format (Keegan et al., 2005), but this report did not include examination of atrial and ventricular lineages.
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