A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics

Garrec, Jean-François Le; Domínguez, Jorge N.; Desgrange, Audrey; Ivanovitch, Kenzo; Raphaël, Etienne; Bangham, Jenny; Torres, Miguel; Coen, Enrico; Mohun, Timothy J.; Meilhac, Sigolène M.

doi:10.7554/elife.28951

Cited by 83 publications

(159 citation statements)

References 85 publications

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“…4A). These further developed into denser crescent-like structures with beating areas, leading to beating epithelial protrusions on the anterior portion of the gastruloids at around 168 h. Similar to mouse embryos (Ivanovitch et al, 2017;Le Garrec et al;Tyser et al, 2016), these phenotypes could be observed in gastruloids within 24 h, and could be aligned to progressive morphological stages of embryonic cardiac development between E7.5 and E8.5 (Fig. 4B).…”

Section: In Vitro Cardiac Development Occurs Through Establishment Ofmentioning

confidence: 60%

Embryonic organoids recapitulate early heart organogenesis

Rossi

Boni²,

Guiet

et al. 2019

Preprint

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Organoids are powerful models for studying tissue development, physiology, and disease. However, current culture systems disrupt the inductive tissue-tissue interactions needed for the complex morphogenetic processes of native organogenesis. Here we show that mouse embryonic stem cells (mESCs) can be coaxed to robustly undergo the fundamental steps of early heart organogenesis with an in vivo-like spatiotemporal fidelity. These axially patterned embryonic organoids support the generation of cardiovascular progenitors, as well as first and second heart field compartments. The cardiac progenitors self-organize into an anterior domain reminiscent of a cardiac crescent before forming a beating cardiac tissue near a primitive gutlike tube, from which it is separated by an endocardial-like layer. These findings unveil the surprising morphogenetic potential of mESCs to execute key aspects of organogenesis through the coordinated development of multiple tissues. This platform could be an excellent tool for studying heart development in unprecedented detail and throughput.

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Section: In Vitro Cardiac Development Occurs Through Establishment Ofmentioning

confidence: 60%

Embryonic organoids recapitulate early heart organogenesis

Rossi

Boni²,

Guiet

et al. 2019

Preprint

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show abstract

“…Nodal expression in the lateral plate mesoderm has been previously reported at 3-6 somite stages (Vincent et al, 2004). However, we found that somitogenesis is not synchronised with heart morphogenesis (Le Garrec et al, 2017), so we re-analysed Nodal expression within the context of heart looping stages. By RT-qPCR of the cardiac region, we found expression of Nodal at E8.5c-d ( Fig.…”

Section: Nodal Is Transiently Active Before Heart Looping At E85c-ementioning

confidence: 88%

“…From 3D (dimensions) reconstructions in the mouse embryo, we have previously characterised the spatiotemporal dynamics of heart looping, and established specific staging criteria. A model for a heart-specific random generator of asymmetry was proposed (Le Garrec et al, 2017). We showed that the heart tube grows between fixed poles, which is compatible with a buckling mechanism, able to generate random deformations.…”

Section: Introductionmentioning

confidence: 83%

“…Within the framework of the model of heart looping that we have proposed previously (Le Garrec et al, 2017), we analysed whether the identified parameters are affected. Heart looping depends on the buckling of the heart tube, growing between fixed poles.…”

Section: Existence Of a Random Generator Of Asymmetry Independent Of mentioning

confidence: 99%

“…Clonal analyses of myocardial cells have shown a differential origin of the pulmonary trunk and aorta from left and right precursors respectively (Lescroart et al, 2010;. In keeping with the spiralling of the great arteries in the mature heart, the outflow tract undergoes a rightward rotation (Bajolle et al, 2006), which follows that of the arterial pole during heart looping (Le Garrec et al, 2017). Regionalisation of the outflow tract prefigures the separation of the great arteries, as marked by Sema3c (Théveniau-Ruissy et al, 2008).…”

Section: Introductionmentioning

confidence: 97%

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Transient Nodal signalling in left precursors coordinates opposed asymmetries shaping the heart loop

Desgrange

Garrec

Bernheim

et al. 2019

Preprint

Self Cite

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The secreted factor Nodal has been shown to be a major left determinant. Although it is associated with severe congenital heart defects, its role in heart morphogenesis has remained poorly understood. Here, we report that Nodal is transiently active in precursors of the mouse heart tube poles, before the morphological changes of heart looping. In conditional mutants, we show that Nodal is not required to initiate asymmetric morphogenesis. We provide evidence of a heart-specific random generator of asymmetry that is independent of Nodal. Using 3D quantifications and simulations, we demonstrate that Nodal functions as a bias of this mechanism: it is required to amplify and coordinate opposed left-right asymmetries at the heart tube poles, thus generating a robust helical shape. We identify downstream effectors of Nodal signalling, regulating asymmetries in cell proliferation, cell differentiation and extra-cellular matrix composition. Our work provides novel insight into how Nodal regulates asymmetric organogenesis.

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4D Bioprinting Shape‐Morphing Tissues in Granular Support Hydrogels: Sculpting Structure and Guiding Maturation

Pramanick,

Hayes,

Sergis

et al. 2024

Adv Funct Materials

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During embryogenesis, organs undergo dynamic shape transformations that sculpt their final shape, composition, and function. Despite this, current organ bioprinting approaches typically employ bioinks that restrict cell‐generated morphogenetic behaviors resulting in structurally static tissues. This work introduces a novel platform that enables the bioprinting of tissues that undergo programmable and predictable 4D shape‐morphing driven by cell‐generated forces. This method utilizes embedded bioprinting to deposit collagen‐hyaluronic acid bioinks within yield‐stress granular support hydrogels that can accommodate and regulate 4D shape‐morphing through their viscoelastic properties. Importantly, precise control over 4D shape‐morphing is possible by modulating factors such as the initial print geometry, cell phenotype, bioink composition, and support hydrogel viscoelasticity. Further, shape‐morphing is found to actively sculpt cell and extracellular matrix alignment along the principal tissue axis through a stress‐avoidance mechanism. To enable predictive design of 4D shape‐morphing patterns, a finite element model is developed that accurately captures shape evolution at both the cellular and tissue levels. Finally, it is demonstrated that programmed 4D shape‐morphing enhances the structural and functional properties of iPSC‐derived heart tissues. This ability to design, predict, and program 4D shape‐morphing holds great potential for engineering organ rudiments that recapitulate morphogenetic processes to sculpt their final shape, composition, and function.

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A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics

Cited by 83 publications

References 85 publications

Embryonic organoids recapitulate early heart organogenesis

Embryonic organoids recapitulate early heart organogenesis

Transient Nodal signalling in left precursors coordinates opposed asymmetries shaping the heart loop

4D Bioprinting Shape‐Morphing Tissues in Granular Support Hydrogels: Sculpting Structure and Guiding Maturation

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