Abstract
From gastrulation to late organogenesis animal development involves many genetic and bio-mechanical interactions between epithelial and mesenchymal tissues. Ectodermal organs, such as hairs, feathers and teeth are well studied examples of organs whose development is based on epithelial-mesenchymal interactions. These develop from a similar primordium through an epithelial folding and its interaction with the mesenchyme. Despite extensive knowledge on the molecular pathways involved, little is known about the role of bio-mechanical processes in the morphogenesis of these organs. We propose a simple computational model for the biomechanics of one such organ, the tooth, and contrast its predictions against cell-tracking experiments, mechanical relaxation experiments and the observed tooth shape changes over developmental time. We found that two biomechanical processes, differential tissue growth and differential cell adhesion, were enough, in the model, for the development of the 3D morphology of the early tooth germ. This was largely determined by the length and direction of growth of the cervical loops, lateral folds of the enamel epithelium. The formation of these cervical loops was found to require accelerated epithelial growth relative to other tissues and their direction of growth depended on specific differential adhesion between the three tooth tissues. These two processes and geometrical constraints in early tooth bud also explained the shape asymmetry between the lateral cervical loops and those forming in the anterior and posterior of the tooth. By performing mechanical perturbations ex vivo and in silico we inferred the distribution and direction of tensile stresses in the mesenchyme that restricted cervical loop lateral growth and forced them to grow downwards. Overall our study suggests detailed quantitative explanations for how bio-mechanical processes lead to specific morphological 3D changes over developmental time.
Highlights
From gastrulation to late organogenesis, animal development involves many examples of reciprocal genetic and biomechanical interactions between epithelial and mesenchymal tissues [1]
As long as the suprabasal layer grows relatively slower than the epithelium, the latter will need to fold in order to keep contact with the former due to their heterotypic adhesion (e.g. S11C Fig, left most column)
High mesenchymal growth prevents epithelial buckling in the central part of the tooth germ and forces the epithelium to fold around the growing mesenchyme (Fig 3D), a process which depends on the epithelial-mesenchymal heterotypic adhesion
Summary
From gastrulation to late organogenesis, animal development involves many examples of reciprocal genetic and biomechanical interactions between epithelial and mesenchymal tissues [1]. Ectodermal organs, such as hairs, feathers, teeth and mammary glands are accessible examples of organs whose development is based on epithelial-mesenchymal interactions. Organogenesis begins with the appearance of local epithelial thickenings, placodes, followed by condensation of the underlying mesenchymal cells. The placode develops into a bud that grows into or out of the mesenchyme ensued by further growth and morphogenesis specific to each organ [2]. In this study we explore this latter question for tooth development as an example ectodermal organ
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