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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

Primary mechanisms in model for c-looping. Schematic diagrams of looping heart tube (HT) in (A) lateral, (B) ventral, and (C) cross-sectional views. (A) Bending of the HT is driven mainly by differential hypertrophic myocardial growth. Longitudinal growth causes the ventral side to elongate (red arrows), while the dorsal side shortens (blue arrows) with the dorsal mesocardium (DM) located at the inner curvature. (B) Asymmetric growth (red arrows) on the cranial sides of the omphalomesenteric veins (OVs) causes a slight rightward twist of the HT, as cytoskeletal contraction on the caudal sides (blue arrows) enhances the OV forces exerted on the HT. (Green dots indicate the original midline of the HT.) (C) The splanchnopleuric membrane (SPL) pushes the HT dorsally (black arrows) into its fully twisted position. AIP, anterior intestinal portal; CT, conotruncus.
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Figure 2: Primary mechanisms in model for c-looping. Schematic diagrams of looping heart tube (HT) in (A) lateral, (B) ventral, and (C) cross-sectional views. (A) Bending of the HT is driven mainly by differential hypertrophic myocardial growth. Longitudinal growth causes the ventral side to elongate (red arrows), while the dorsal side shortens (blue arrows) with the dorsal mesocardium (DM) located at the inner curvature. (B) Asymmetric growth (red arrows) on the cranial sides of the omphalomesenteric veins (OVs) causes a slight rightward twist of the HT, as cytoskeletal contraction on the caudal sides (blue arrows) enhances the OV forces exerted on the HT. (Green dots indicate the original midline of the HT.) (C) The splanchnopleuric membrane (SPL) pushes the HT dorsally (black arrows) into its fully twisted position. AIP, anterior intestinal portal; CT, conotruncus.

Mentions: Based on these prior studies, the main forces that drive normal c-looping in our proposed model are differential growth in the HT and OVs, and pressure exerted by the SPL. Differential growth causes the HT to bend (Figure 2A) and the OVs to push against the HT, initiating a slight rightward twist (Figure 2B). Then, SPL pressure enhances the torsion as the HT continues to bend (Figure 2C). The model also includes growth of CJ, tension in the DM, active changes in myocardial cell shape, cytoskeletal contraction around the AIP, and elongation of the HT caused by OV fusion.1


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)

Primary mechanisms in model for c-looping. Schematic diagrams of looping heart tube (HT) in (A) lateral, (B) ventral, and (C) cross-sectional views. (A) Bending of the HT is driven mainly by differential hypertrophic myocardial growth. Longitudinal growth causes the ventral side to elongate (red arrows), while the dorsal side shortens (blue arrows) with the dorsal mesocardium (DM) located at the inner curvature. (B) Asymmetric growth (red arrows) on the cranial sides of the omphalomesenteric veins (OVs) causes a slight rightward twist of the HT, as cytoskeletal contraction on the caudal sides (blue arrows) enhances the OV forces exerted on the HT. (Green dots indicate the original midline of the HT.) (C) The splanchnopleuric membrane (SPL) pushes the HT dorsally (black arrows) into its fully twisted position. AIP, anterior intestinal portal; CT, conotruncus.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Primary mechanisms in model for c-looping. Schematic diagrams of looping heart tube (HT) in (A) lateral, (B) ventral, and (C) cross-sectional views. (A) Bending of the HT is driven mainly by differential hypertrophic myocardial growth. Longitudinal growth causes the ventral side to elongate (red arrows), while the dorsal side shortens (blue arrows) with the dorsal mesocardium (DM) located at the inner curvature. (B) Asymmetric growth (red arrows) on the cranial sides of the omphalomesenteric veins (OVs) causes a slight rightward twist of the HT, as cytoskeletal contraction on the caudal sides (blue arrows) enhances the OV forces exerted on the HT. (Green dots indicate the original midline of the HT.) (C) The splanchnopleuric membrane (SPL) pushes the HT dorsally (black arrows) into its fully twisted position. AIP, anterior intestinal portal; CT, conotruncus.
Mentions: Based on these prior studies, the main forces that drive normal c-looping in our proposed model are differential growth in the HT and OVs, and pressure exerted by the SPL. Differential growth causes the HT to bend (Figure 2A) and the OVs to push against the HT, initiating a slight rightward twist (Figure 2B). Then, SPL pressure enhances the torsion as the HT continues to bend (Figure 2C). The model also includes growth of CJ, tension in the DM, active changes in myocardial cell shape, cytoskeletal contraction around the AIP, and elongation of the HT caused by OV fusion.1

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