1. Molar Bud-to-Cap Transition Is Proliferation Independent
- Author
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Rupali Lav, Shuntaro Yamada, Abigail S. Tucker, Jingjing Li, and Jeremy B. Green
- Subjects
0301 basic medicine ,Molar ,Pediatric Research Initiative ,1.1 Normal biological development and functioning ,Mesenchyme ,morphogenesis ,Odontogenic Epithelium ,Mesoderm ,developmental biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Underpinning research ,Pregnancy ,cell biology ,medicine ,Animals ,Developmental ,General Dentistry ,Tooth Germs ,Cell Proliferation ,Pediatric ,morphometrics ,Transition (genetics) ,Chemistry ,tooth development ,Gene Expression Regulation, Developmental ,Tooth Germ ,Research Reports ,Biological ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Dentistry ,Congenital Structural Anomalies ,Odontogenesis ,Female ,basal constriction ,030217 neurology & neurosurgery - Abstract
Tooth germs undergo a series of dynamic morphologic changes through bud, cap, and bell stages, in which odontogenic epithelium continuously extends into the underlying mesenchyme. During the transition from the bud stage to the cap stage, the base of the bud flattens and then bends into a cap shape whose edges are referred to as “cervical loops.” Although genetic mechanisms for cap formation have been well described, little is understood about the morphogenetic mechanisms. Computer modeling and cell trajectory tracking have suggested that the epithelial bending is driven purely by differential cell proliferation and adhesion in different parts of the tooth germ. Here, we show that, unexpectedly, inhibition of cell proliferation did not prevent bud-to-cap morphogenesis. We quantified cell shapes and actin and myosin distributions in different parts of the tooth epithelium at the critical stages and found that these are consistent with basal relaxation in the forming cervical loops and basal constriction around enamel knot at the center of the cap. Inhibition of focal adhesion kinase, which is required for basal constriction in other systems, arrested the molar explant morphogenesis at the bud stage. Together, these results show that the bud-to-cap transition is largely proliferation independent, and we propose that it is driven by classic actomyosin-driven cell shape–dependent mechanisms. We discuss how these results can be reconciled with the previous models and data.
- Published
- 2019
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