The "Mickey Mouse Heart" describes patients with a combination of HFpEF, massive biatrial dilatation and dilatation of the mitral- and tricuspid annulus, atrial fibrillation and severe mitral- and tricuspid regurgitation. To assess the overall growth of the forming HT, we measured cTnnT+ tissue volume in segmented z-stacks, at the stages described above ( Figure 1I and Figure 1—source data 1).

In the future, it will be interesting to explore whether novel non-toxic index-matching media compatible with embryo viability ( Boothe et al.

half) 3D reconstruction at three time points based of the eGFP signal (green) and red-labeled cells located in the splanchnic mesoderm. B–G) Immunostaining for cTnnT (red) and Dapi (blue) showing six consecutive stages during cardiac differentiation ( B–D) and HT morphogenesis ( E–G). Differentiation of cardiac progenitors is thus accompanied by changes in cell shape and detachment from the endoderm. Thus, SHF cells do not differentiate during the 5–7 hr period when morphogenesis of the open HT takes place, but coordinately start differentiation at different regions of the HT during dorsal closure.

Although these cells migrate antero-medially relative to the underlying more static endodermal cells (see endodermal cell highlighted by the red arrow from t = 69 m in Video 9), they do not contribute to the HT during the observation period. It is therefore challenging to accurately track cardiac differentiation by the increase of GFP levels there ( Figure 8—figure supplement 1A–A’’, from around 200 μm depth, see next section).Every scene is so beautiful described and animated; the intense scenes and the backdrop of Old Bristol dance on the page as if it were all happening in an enchanted diorama. In all the embryos immunostained for cTnnT, the yolk sack signal is non-specific background (indicated by an asterisks).