Early epithelial signaling center governs tooth budding morphogenesis

• Published in: The Journal of cell biology Vol. 214; no. 6; pp. 753 - 767
• Main Authors: Ahtiainen, Laura, Uski, Isa, Thesleff, Irma, Mikkola, Marja L.
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 12.09.2016; The Rockefeller University Press
• Subjects: Animals; Cell Movement; Cell Proliferation; Cellular biology; Ectodysplasins - genetics; Ectodysplasins - metabolism; Edar Receptor - genetics; Edar Receptor - metabolism; Epithelial Cells - metabolism; Epithelial Cells - physiology; G1 Phase; Gene expression; Gene Expression Regulation, Developmental; Genotype; Gestational Age; Inactivation; Incisor - embryology; Incisor - metabolism; Mice, Transgenic; Microscopy, Confocal; Morphogenesis; NF-kappa B - genetics; NF-kappa B - metabolism; Organ Size; Phenotype; Signal Transduction
• ISSN: 0021-9525; 1540-8140; 1540-8140
• DOI: 10.1083/jcb.201512074

During organogenesis, cell fate specification and patterning are regulated by signaling centers, specialized clusters of morphogen-expressing cells. In many organs, initiation of development is marked by bud formation, but the cellular mechanisms involved are ill defined. Here, we use the mouse incisor tooth as a model to study budding morphogenesis. We show that a group of nonproliferative epithelial cells emerges in the early tooth primordium and identify these cells as a signaling center. Confocal live imaging of tissue explants revealed that although these cells reorganize dynamically, they do not reenter the cell cycle or contribute to the growing tooth bud. Instead, budding is driven by proliferation of the neighboring cells. We demonstrate that the activity of the ectodysplasin/Edar/nuclear factor κB pathway is restricted to the signaling center, and its inactivation leads to fewer quiescent cells and a smaller bud. These data functionally link the signaling center size to organ size and imply that the early signaling center is a prerequisite for budding morphogenesis.