Differential tissue growth and cell adhesion alone drive early tooth morphogenesis : An ex vivo and in silico study
Marin-Riera, Miquel (University of Helsinki, Finland)
Moustakas-Verho, Jacqueline (University of Helsinki, Finland)
Savriama, Yoland (University of Helsinki, Finland)
Jernvall, Jukka (University of Helsinki, Finland)
Salazar Ciudad, Isaac (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Date:	2018
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.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2013FI-B00439
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PLoS computational biology, Vol. 14 (february 2018) , ISSN 1553-7358

DOI: 10.1371/journal.pcbi.1005981
PMID: 29481561

26 p, 30.5 MB

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