A Chemomechanical Model for Regulation of Contractility in the Embryonic Brain Tube.

Morphogenesis is regulated by genetic, biochemical, and biomechanical factors, but the feedback controlling the interactions between these factors remains poorly understood. A previous study has found that compressing the brain tube of the early chick embryo induces changes in contractility and nuclear shape in the neuroepithelial wall. Assuming this response involves mechanical feedback, we use experiments and computational modeling to investigate a hypothetical mechanism behind the observed behavior.

Molecular and mechanical signals determine morphogenesis of the cerebral hemispheres in the chicken embryo.

During embryonic development, the telecephalon undergoes extensive growth and cleaves into right and left cerebral hemispheres. Although molecular signals have been implicated in this process and linked to congenital abnormalities, few studies have examined the role of mechanical forces. In this study, we quantified morphology, cell proliferation and tissue growth in the forebrain of chicken embryos during Hamburger-Hamilton stages 17-21.

Reduced embryonic blood flow impacts extracellular matrix deposition in the maturing aorta.

Background: Perturbations to embryonic hemodynamics are known to adversely affect cardiovascular development. Vitelline vein ligation (VVL) is a model of reduced placental blood flow used to induce cardiac defects in early chick embryo development. The effect of these hemodynamic interventions on maturing elastic arteries is largely unknown.

Dynamic patterns of cortical expansion during folding of the preterm human brain.

During the third trimester of human brain development, the cerebral cortex undergoes dramatic surface expansion and folding. Physical models suggest that relatively rapid growth of the cortical gray matter helps drive this folding, and structural data suggest that growth may vary in both space (by region on the cortical surface) and time. In this study, we propose a unique method to estimate local growth from sequential cortical reconstructions.

How mechanical forces shape the developing eye.

In the vertebrate embryo, the eyes develop from optic vesicles that grow laterally outward from the brain tube and contact the overlying surface ectoderm. Within the region of contact, each optic vesicle and the surface ectoderm thicken to form placodes, which then invaginate to create the optic cup and lens pit, respectively. Eventually, the optic cup becomes the retina, while the lens pit closes to form the lens vesicle.

Apoptosis generates mechanical forces that close the lens vesicle in the chick embryo.

During the initial stages of eye development, optic vesicles grow laterally outward from both sides of the forebrain and come into contact with the surrounding surface ectoderm (SE). Within the region of contact, these layers then thicken locally to create placodes and invaginate to form the optic cup (primitive retina) and lens vesicle (LV), respectively. This paper examines the biophysical mechanisms involved in LV formation, which consists of three phases: (1) lens placode formation; (2) invagination to create the lens pit (LP); and (3) closure to form a complete ellipsoidally shaped LV.

A new hypothesis for foregut and heart tube formation based on differential growth and actomyosin contraction.

For decades, it was commonly thought that the bilateral heart fields in the early embryo fold directly towards the midline, where they meet and fuse to create the primitive heart tube. Recent studies have challenged this view, however, suggesting that the heart fields fold diagonally. As early foregut and heart tube morphogenesis are intimately related, this finding also raises questions concerning the traditional view of foregut formation.

Contraction and stress-dependent growth shape the forebrain of the early chicken embryo.

During early vertebrate development, local constrictions, or sulci, form to divide the forebrain into the diencephalon, telencephalon, and optic vesicles. These partitions are maintained and exaggerated as the brain tube inflates, grows, and bends. Combining quantitative experiments on chick embryos with computational modeling, we investigated the biophysical mechanisms that drive these changes in brain shape.

Tissue growth constrained by extracellular matrix drives invagination during optic cup morphogenesis.

In the early embryo, the eyes form initially as relatively spherical optic vesicles (OVs) that protrude from both sides of the brain tube. Each OV grows until it contacts and adheres to the overlying surface ectoderm (SE) via an extracellular matrix (ECM) that is secreted by the SE and OV. The OV and SE then thicken and bend inward (invaginate) to create the optic cup (OC) and lens vesicle, respectively.

How the embryonic chick brain twists.

During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left-right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination of experiments, a physical model of the embryonic morphology and mechanics analysis that the vitelline membrane (VM) exerts an external load on the brain that drives torsion.

Why is cytoskeletal contraction required for cardiac fusion before but not after looping begins?

Cytoskeletal contraction is crucial to numerous morphogenetic processes, but its role in early heart development is poorly understood. Studies in chick embryos have shown that inhibiting myosin-II-based contraction prior to Hamburger-Hamilton (HH) stage 10 (33 h incubation) impedes fusion of the mesodermal heart fields that create the primitive heart tube (HT), as well as the ensuing process of cardiac looping. If contraction is inhibited at or after looping begins at HH10, however, fusion and looping proceed relatively normally.

Mechanical effects of the surface ectoderm on optic vesicle morphogenesis in the chick embryo.

Precise shaping of the eye is crucial for proper vision. Here, we use experiments on chick embryos along with computational models to examine the mechanical factors involved in the formation of the optic vesicles (OVs), which grow outward from the forebrain of the early embryo. First, mechanical dissections were used to remove the surface ectoderm (SE), a membrane that contacts the outer surfaces of the OVs.

Probing regional mechanical properties of embryonic tissue using microindentation and optical coherence tomography.

Physical forces regulate morphogenetic movements and the mechanical properties of embryonic tissues during development. Such quantities are closely interrelated, as increases in material stiffness can limit force-induced deformations and vice versa. Here we present a minimally invasive method to quantify spatiotemporal changes in mechanical properties during morphogenesis.

Simple and accurate methods for quantifying deformation, disruption, and development in biological tissues.

When mechanical factors underlie growth, development, disease or healing, they often function through local regions of tissue where deformation is highly concentrated. Current optical techniques to estimate deformation can lack precision and accuracy in such regions due to challenges in distinguishing a region of concentrated deformation from an error in displacement tracking. Here, we present a simple and general technique for improving the accuracy and precision of strain estimation and an associated technique for distinguishing a concentrated deformation from a tracking error.

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

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.

Morphomechanics: transforming tubes into organs.

After decades focusing on the molecular and genetic aspects of organogenesis, researchers are showing renewed interest in the physical mechanisms that create organs. This review deals with the mechanical processes involved in constructing the heart and brain, concentrating primarily on cardiac looping, shaping of the primitive brain tube, and folding of the cerebral cortex. Recent studies suggest that differential growth drives large-scale shape changes in all three problems, causing the heart and brain tubes to bend and the cerebral cortex to buckle.

Bending of the looping heart: differential growth revisited.

In the early embryo, the primitive heart tube (HT) undergoes the morphogenetic process of c-looping as it bends and twists into a c-shaped tube. Despite intensive study for nearly a century, the physical forces that drive looping remain poorly understood. This is especially true for the bending component, which is the focus of this paper.

Computational and experimental study of the mechanics of embryonic wound healing.

Wounds in the embryo show a remarkable ability to heal quickly without leaving a scar. Previous studies have found that an actomyosin ring (purse string) forms around the wound perimeter and contracts to close the wound over the course of several dozens of minutes. Here, we report experiments that reveal an even faster mechanism which remarkably closes wounds by more than 50% within the first 30s.

Regional differences in actomyosin contraction shape the primary vesicles in the embryonic chicken brain.

In the early embryo, the brain initially forms as a relatively straight, cylindrical epithelial tube composed of neural stem cells. The brain tube then divides into three primary vesicles (forebrain, midbrain, hindbrain), as well as a series of bulges (rhombomeres) in the hindbrain. The boundaries between these subdivisions have been well studied as regions of differential gene expression, but the morphogenetic mechanisms that generate these constrictions are not well understood.

Computational models for mechanics of morphogenesis.

In the developing embryo, tissues differentiate, deform, and move in an orchestrated manner to generate various biological shapes driven by the complex interplay between genetic, epigenetic, and environmental factors. Mechanics plays a key role in regulating and controlling morphogenesis, and quantitative models help us understand how various mechanical forces combine to shape the embryo. Models allow for the quantitative, unbiased testing of physical mechanisms, and when used appropriately, can motivate new experimentaldirections.

On integrating experimental and theoretical models to determine physical mechanisms of morphogenesis.

Researchers in developmental biology are increasingly recognizing the value of theoretical models in studies of morphogenesis. However, creating and testing realistic quantitative models for morphogenetic processes can be an extremely challenging task. The focus of this paper is on models for the mechanics of morphogenesis.

Not just inductive: a crucial mechanical role for the endoderm during heart tube assembly.

The heart is the first functioning organ to form during development. During gastrulation, the cardiac progenitors reside in the lateral plate mesoderm but maintain close contact with the underlying endoderm. In amniotes, these bilateral heart fields are initially organized as a pair of flat epithelia that move towards the embryonic midline and fuse above the anterior intestinal portal (AIP) to form the heart tube.

Viscoelastic material properties of the myocardium and cardiac jelly in the looping chick heart.

Accurate material properties of developing embryonic tissues are a crucial factor in studies of the mechanics of morphogenesis. In the present work, we characterize the viscoelastic material properties of the looping heart tube in the chick embryo through nonlinear finite element modeling and microindentation experiments. Both hysteresis and ramp-hold experiments were performed on the intact heart and isolated cardiac jelly (extracellular matrix).