Limits...
Bending and twisting the embryonic heart: a computational model for c-looping based on realistic geometry.

Shi Y, Yao J, Young JM, Fee JA, Perucchio R, Taber LA - Front Physiol (2014)

Bottom Line: The behavior of the model is in reasonable agreement with available experimental data from control and perturbed embryos, offering support for our hypothesis.The results also suggest, however, that several other mechanisms contribute secondarily to normal looping, and we speculate that these mechanisms play backup roles when looping is perturbed.Finally, some outstanding questions are discussed for future study.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Washington University St. Louis, MO, USA.

ABSTRACT
The morphogenetic process of cardiac looping transforms the straight heart tube into a curved tube that resembles the shape of the future four-chambered heart. Although great progress has been made in identifying the molecular and genetic factors involved in looping, the physical mechanisms that drive this process have remained poorly understood. Recent work, however, has shed new light on this complicated problem. After briefly reviewing the current state of knowledge, we propose a relatively comprehensive hypothesis for the mechanics of the first phase of looping, termed c-looping, as the straight heart tube deforms into a c-shaped tube. According to this hypothesis, differential hypertrophic growth in the myocardium supplies the main forces that cause the heart tube to bend ventrally, while regional growth and cytoskeletal contraction in the omphalomesenteric veins (primitive atria) and compressive loads exerted by the splanchnopleuric membrane drive rightward torsion. A computational model based on realistic embryonic heart geometry is used to test the physical plausibility of this hypothesis. The behavior of the model is in reasonable agreement with available experimental data from control and perturbed embryos, offering support for our hypothesis. The results also suggest, however, that several other mechanisms contribute secondarily to normal looping, and we speculate that these mechanisms play backup roles when looping is perturbed. Finally, some outstanding questions are discussed for future study.

No MeSH data available.


Related in: MedlinePlus

Effects of removing omphalomesenteric veins (OVs) or heart tube (HT). (A–H) Bright-field images of experimental perturbations reprinted from Ramasubramanian et al. (2008) (A–F) and Kidokoro et al. (2008) (G,H) with permissions of ASME and Wiley. (A,C,E,G) HH10- hearts with (A) the left OV, (C) the right OV, (E) both OVs, or (G) the HT removed. For access to the heart, the splanchnopleure was removed first. Black lines denote the cuts. To help visualize rotation, fluorescent labels were injected along the ventral midline of the heart. (B,D,F,H) The same hearts after 12 hr of culture. White dotted lines in (B) and (F) outline the inner curvature of the HT. (A′–H′) Corresponding finite-element simulations. The model predicts all of the final shapes reasonably well, including the leftward looping (B,B′). Note that a portion of the HT [black dotted line in (H)] regrew above the interventricular grooves [arrowheads in (G)] in the experiment through OV fusion, which is not included in the model (H′). Scale bar: 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4129494&req=5

Figure 10: Effects of removing omphalomesenteric veins (OVs) or heart tube (HT). (A–H) Bright-field images of experimental perturbations reprinted from Ramasubramanian et al. (2008) (A–F) and Kidokoro et al. (2008) (G,H) with permissions of ASME and Wiley. (A,C,E,G) HH10- hearts with (A) the left OV, (C) the right OV, (E) both OVs, or (G) the HT removed. For access to the heart, the splanchnopleure was removed first. Black lines denote the cuts. To help visualize rotation, fluorescent labels were injected along the ventral midline of the heart. (B,D,F,H) The same hearts after 12 hr of culture. White dotted lines in (B) and (F) outline the inner curvature of the HT. (A′–H′) Corresponding finite-element simulations. The model predicts all of the final shapes reasonably well, including the leftward looping (B,B′). Note that a portion of the HT [black dotted line in (H)] regrew above the interventricular grooves [arrowheads in (G)] in the experiment through OV fusion, which is not included in the model (H′). Scale bar: 200 μm.

Mentions: In other experiments, Ramasubramanian et al. (2008) removed the SPL and either one or both OVs. After 12 h of culture, the heart looped leftward when the left OV was removed and rightward when either the right OV or both OVs were removed (Figures 10A–F). These results suggest that looping direction can be determined by unbalanced lateral forces exerted by the OVs, and, without the counterbalancing effects of the dissected vein, the remaining vein pushes the HT to the opposite side. Our model reproduces all of these results reasonably well, including the left looping case, although there are some discrepancies in the morphology of the remaining vein (Figures 10A′–F′).


Bending and twisting the embryonic heart: a computational model for c-looping based on realistic geometry.

Shi Y, Yao J, Young JM, Fee JA, Perucchio R, Taber LA - Front Physiol (2014)

Effects of removing omphalomesenteric veins (OVs) or heart tube (HT). (A–H) Bright-field images of experimental perturbations reprinted from Ramasubramanian et al. (2008) (A–F) and Kidokoro et al. (2008) (G,H) with permissions of ASME and Wiley. (A,C,E,G) HH10- hearts with (A) the left OV, (C) the right OV, (E) both OVs, or (G) the HT removed. For access to the heart, the splanchnopleure was removed first. Black lines denote the cuts. To help visualize rotation, fluorescent labels were injected along the ventral midline of the heart. (B,D,F,H) The same hearts after 12 hr of culture. White dotted lines in (B) and (F) outline the inner curvature of the HT. (A′–H′) Corresponding finite-element simulations. The model predicts all of the final shapes reasonably well, including the leftward looping (B,B′). Note that a portion of the HT [black dotted line in (H)] regrew above the interventricular grooves [arrowheads in (G)] in the experiment through OV fusion, which is not included in the model (H′). Scale bar: 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4129494&req=5

Figure 10: Effects of removing omphalomesenteric veins (OVs) or heart tube (HT). (A–H) Bright-field images of experimental perturbations reprinted from Ramasubramanian et al. (2008) (A–F) and Kidokoro et al. (2008) (G,H) with permissions of ASME and Wiley. (A,C,E,G) HH10- hearts with (A) the left OV, (C) the right OV, (E) both OVs, or (G) the HT removed. For access to the heart, the splanchnopleure was removed first. Black lines denote the cuts. To help visualize rotation, fluorescent labels were injected along the ventral midline of the heart. (B,D,F,H) The same hearts after 12 hr of culture. White dotted lines in (B) and (F) outline the inner curvature of the HT. (A′–H′) Corresponding finite-element simulations. The model predicts all of the final shapes reasonably well, including the leftward looping (B,B′). Note that a portion of the HT [black dotted line in (H)] regrew above the interventricular grooves [arrowheads in (G)] in the experiment through OV fusion, which is not included in the model (H′). Scale bar: 200 μm.
Mentions: In other experiments, Ramasubramanian et al. (2008) removed the SPL and either one or both OVs. After 12 h of culture, the heart looped leftward when the left OV was removed and rightward when either the right OV or both OVs were removed (Figures 10A–F). These results suggest that looping direction can be determined by unbalanced lateral forces exerted by the OVs, and, without the counterbalancing effects of the dissected vein, the remaining vein pushes the HT to the opposite side. Our model reproduces all of these results reasonably well, including the left looping case, although there are some discrepancies in the morphology of the remaining vein (Figures 10A′–F′).

Bottom Line: The behavior of the model is in reasonable agreement with available experimental data from control and perturbed embryos, offering support for our hypothesis.The results also suggest, however, that several other mechanisms contribute secondarily to normal looping, and we speculate that these mechanisms play backup roles when looping is perturbed.Finally, some outstanding questions are discussed for future study.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Washington University St. Louis, MO, USA.

ABSTRACT
The morphogenetic process of cardiac looping transforms the straight heart tube into a curved tube that resembles the shape of the future four-chambered heart. Although great progress has been made in identifying the molecular and genetic factors involved in looping, the physical mechanisms that drive this process have remained poorly understood. Recent work, however, has shed new light on this complicated problem. After briefly reviewing the current state of knowledge, we propose a relatively comprehensive hypothesis for the mechanics of the first phase of looping, termed c-looping, as the straight heart tube deforms into a c-shaped tube. According to this hypothesis, differential hypertrophic growth in the myocardium supplies the main forces that cause the heart tube to bend ventrally, while regional growth and cytoskeletal contraction in the omphalomesenteric veins (primitive atria) and compressive loads exerted by the splanchnopleuric membrane drive rightward torsion. A computational model based on realistic embryonic heart geometry is used to test the physical plausibility of this hypothesis. The behavior of the model is in reasonable agreement with available experimental data from control and perturbed embryos, offering support for our hypothesis. The results also suggest, however, that several other mechanisms contribute secondarily to normal looping, and we speculate that these mechanisms play backup roles when looping is perturbed. Finally, some outstanding questions are discussed for future study.

No MeSH data available.


Related in: MedlinePlus