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 external constraints on heart tube (HT). (A–D) Bright-field images of experimental perturbations reprinted from Voronov et al. (2004) with permission of Elsevier. (A′–D′) Corresponding finite-element simulations. (A,A′) Straight HT at HH10-. To help visualize rotation, fluorescent labels were injected along the lateral sides of the HT in the experiment, and artificial labels are placed at similar locations in the model. (B,B′) Same heart at HH12 after 6 h of culture. As the heart rotates rightward, labels on the right (black numbers) and left (white numbers) sides of the HT move toward the dorsal and ventral sides, respectively. The model captures this phenomenon, as the labels originally on the right side now become invisible (dotted circles). (C,C′) Same heart at HH12 after removal of the splanchnopleure (SPL). In both the experiment and model, most rotation disappears as heart untwists, but heart remains bent slightly toward the right. (D,D′) Heart in (C) after transverse dissection of conotruncus (CT, black arrow) and longitudinal dissection of DM [brace in (C) shows length of the cut]. In both experiment and model, the HT tilts toward the right. In addition, the interventricular groove (white arrowhead) smooths out as the heart unbends. Scale bar: 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: Effects of removing external constraints on heart tube (HT). (A–D) Bright-field images of experimental perturbations reprinted from Voronov et al. (2004) with permission of Elsevier. (A′–D′) Corresponding finite-element simulations. (A,A′) Straight HT at HH10-. To help visualize rotation, fluorescent labels were injected along the lateral sides of the HT in the experiment, and artificial labels are placed at similar locations in the model. (B,B′) Same heart at HH12 after 6 h of culture. As the heart rotates rightward, labels on the right (black numbers) and left (white numbers) sides of the HT move toward the dorsal and ventral sides, respectively. The model captures this phenomenon, as the labels originally on the right side now become invisible (dotted circles). (C,C′) Same heart at HH12 after removal of the splanchnopleure (SPL). In both the experiment and model, most rotation disappears as heart untwists, but heart remains bent slightly toward the right. (D,D′) Heart in (C) after transverse dissection of conotruncus (CT, black arrow) and longitudinal dissection of DM [brace in (C) shows length of the cut]. In both experiment and model, the HT tilts toward the right. In addition, the interventricular groove (white arrowhead) smooths out as the heart unbends. Scale bar: 200 μm.

Mentions: Voronov et al. (2004) have shown that when the SPL is removed from an HH12 heart, the HT loses most of its rotation (Figures 9A–C; see also Supplementary Figure S3A). Then, after the conotruncus and DM are severed, the HT tilts to the right (Figure 9D). Our simulations for these dissections produced similar results (Figures 9A′–D′).


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 external constraints on heart tube (HT). (A–D) Bright-field images of experimental perturbations reprinted from Voronov et al. (2004) with permission of Elsevier. (A′–D′) Corresponding finite-element simulations. (A,A′) Straight HT at HH10-. To help visualize rotation, fluorescent labels were injected along the lateral sides of the HT in the experiment, and artificial labels are placed at similar locations in the model. (B,B′) Same heart at HH12 after 6 h of culture. As the heart rotates rightward, labels on the right (black numbers) and left (white numbers) sides of the HT move toward the dorsal and ventral sides, respectively. The model captures this phenomenon, as the labels originally on the right side now become invisible (dotted circles). (C,C′) Same heart at HH12 after removal of the splanchnopleure (SPL). In both the experiment and model, most rotation disappears as heart untwists, but heart remains bent slightly toward the right. (D,D′) Heart in (C) after transverse dissection of conotruncus (CT, black arrow) and longitudinal dissection of DM [brace in (C) shows length of the cut]. In both experiment and model, the HT tilts toward the right. In addition, the interventricular groove (white arrowhead) smooths out as the heart unbends. Scale bar: 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: Effects of removing external constraints on heart tube (HT). (A–D) Bright-field images of experimental perturbations reprinted from Voronov et al. (2004) with permission of Elsevier. (A′–D′) Corresponding finite-element simulations. (A,A′) Straight HT at HH10-. To help visualize rotation, fluorescent labels were injected along the lateral sides of the HT in the experiment, and artificial labels are placed at similar locations in the model. (B,B′) Same heart at HH12 after 6 h of culture. As the heart rotates rightward, labels on the right (black numbers) and left (white numbers) sides of the HT move toward the dorsal and ventral sides, respectively. The model captures this phenomenon, as the labels originally on the right side now become invisible (dotted circles). (C,C′) Same heart at HH12 after removal of the splanchnopleure (SPL). In both the experiment and model, most rotation disappears as heart untwists, but heart remains bent slightly toward the right. (D,D′) Heart in (C) after transverse dissection of conotruncus (CT, black arrow) and longitudinal dissection of DM [brace in (C) shows length of the cut]. In both experiment and model, the HT tilts toward the right. In addition, the interventricular groove (white arrowhead) smooths out as the heart unbends. Scale bar: 200 μm.
Mentions: Voronov et al. (2004) have shown that when the SPL is removed from an HH12 heart, the HT loses most of its rotation (Figures 9A–C; see also Supplementary Figure S3A). Then, after the conotruncus and DM are severed, the HT tilts to the right (Figure 9D). Our simulations for these dissections produced similar results (Figures 9A′–D′).

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