Physical And Mechanical Forces That Shape Heart Tube In The Chick Embryo

In the embryo, the heart is initially a simple tubular structure that undergoes complex morphological changes. This work focuses on the mechanisms that create the heart tube (HT). The early embryo is composed of three relatively flat primary germ layers called endoderm, mesoderm, and ectoderm. Endoderm and pre-cardiac cells located within bilateral regions of the mesoderm called heart fields (HFs) fold and fuse along the embryonic midline. Then both layers lengthen axially as the anterior intestinal portal (AIP) moves downward. Finally, the fused HFs thicken and expand to create the HT. Here, we combine experiments on chick embryos with computational modeling to explore physical mechanisms of heart tube formation. According to our hypothesis, differential anisotropic growth between mesoderm and endoderm drives ventral folding, and contraction along the AIP generates tension to elongate the HT. We test this hypothesis using biochemical perturbations of cell proliferation and contractility, as well as computational modeling. In embryos exposed to the mitotic inhibitor aphidicolin, little or no folding occurred, confirming that cell proliferation is required to initiate folding of HFs. To determine the effects of actomyosin contraction, we cultured Hamburger-Hamilton stage 5 embryos in media containing the myosin inhibitor blebbistatin. During incubation, folding occurred in treated embryos, but AIP descension proceeded at a progressively slower rate, showing that AIP downward motion is generated mainly by AIP contraction. Simulating these mechanisms in our computational model produces morphology in reasonable agreement with experiments. For the last phase, adding circumferential growth causes the HF to expand, creating the primitive HT, while radial growth increases the thickness of the heart wall. In conclusion, results of our study support our hypothesis for the creation of the heart tube.