Mechanics of head fold formation: investigating tissue-level forces during early development

Abstract

SUMMARYDuring its earliest stages, the avian embryo is approximately planar. Through a complex series of folds, this flat geometry is transformed into the intricate three-dimensional structure of the developing organism. Formation of the head fold (HF) is the first step in this cascading sequence of out-of-plane tissue folds. The HF establishes the anterior extent of the embryo and initiates heart, foregut and brain development. Here, we use a combination of computational modeling and experiments to determine the physical forces that drive HF formation. Using chick embryos cultured ex ovo, we measured: (1) changes in tissue morphology in living embryos using optical coherence tomography (OCT); (2) morphogenetic strains (deformations) through the tracking of tissue labels; and (3) regional tissue stresses using changes in the geometry of circular wounds punched through the blastoderm. To determine the physical mechanisms that generate the HF, we created a three-dimensional computational model of the early embryo, consisting of pseudoelastic plates representing the blastoderm and vitelline membrane. Based on previous experimental findings, we simulated the following morphogenetic mechanisms: (1) convergent extension in the neural plate (NP); (2) cell wedging along the anterior NP border; and (3) autonomous in-plane deformations outside the NP. Our numerical predictions agree relatively well with the observed morphology, as well as with our measured stress and strain distributions. The model also predicts the abnormal tissue geometries produced when development is mechanically perturbed. Taken together, the results suggest that the proposed morphogenetic mechanisms provide the main tissue-level forces that drive HF formation.

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

“…Approximately 24 hours into the 21-day incubation period of the chick, the head fold forms at the anterior end of the blastoderm (Varner et al, 2010) and initiates formation of the foregut and anterior intestinal portal (AIP) (Bellairs, 1953;Stalsberg and DeHaan, 1968;Varner et al, 2010). At this stage of development (i.e.…”

“…In recent years, groups of developmental biologists, physicists and engineers have been paying renewed attention to the mechanics of morphogenesis: how forces are generated in the embryo (Hutson et al, 2003;Rauzi et al, 2008;Martin et al, 2009;Martin, 2010;Wozniak and Chen, 2009), how those forces are integrated into tissue-level deformations 1685 RESEARCH ARTICLE Mechanical role for endoderm (Ramasubramanian et al, 2006;Chen and Brodland, 2008;Martin et al, 2010;Varner et al, 2010;Brodland et al, 2010) and how they might regulate both cytoskeletal dynamics (Bertet et al, 2004;Fernandez-Gonzalez et al, 2009;Pouille et al, 2009;Zhou et al, 2010;Filas et al, 2011) and regional gene expression (Farge, 2003;Desprat et al, 2008). Here, we have characterized some of the mechanical forces that drive heart tube assembly in the avian embryo.…”

“…The tensor G changes the zero-stress configuration of each material element (akin to thermal contraction of a passive material), and F* generates mechanical stress by both enforcing geometric compatibility between material elements and accounting for the elastic response of the material to any applied loads. This theory has been used to model several different morphogenetic processes, including head fold formation (Varner et al, 2010) and cardiac c-looping (Voronov et al, 2004;Ramasubramanian et al, 2006) in the chick embryo, cortical folding in the developing ferret brain (Xu et al, 2010), and ventral furrow formation in Drosophila (Muñoz et al, 2007;Muñoz et al, 2010). …”

Cellular and physical mechanisms of branching morphogenesis

“…This approach was strictly focused on behaviors at the tissue level, and any cell-or molecular-level details were 'lumped' into model parameters. This framework has been used to simulate several morphogenetic processes, including head-fold formation (Varner et al, 2010) and cardiac looping (Shi et al, 2014;Voronov et al, 2004). Importantly, the observed patterns of epithelial proliferation in the chicken lung were not sufficient to simulate the observed changes in epithelial morphology during branching morphogenesis (Kim et al, 2013).…”

Steering a changing course

“…This is probably because more and more scientists from other non-biological backgrounds, such as physics, are joining this emerging field. This year, we have published some excellent papers in this field, covering a broad variety of topics, from the analysis of mechanical properties (Varner et al, 2010) to in silico evolution (François and Siggia, 2010), and to modelling DNA-target recognition (Scialdone and Nicodemi, 2010). Although some of these papers might make for a challenging read, we do encourage their authors to write them in the most accessible way.…”