Myosin II mediates Shh signals to shape dental epithelia via control of cell adhesion and movement.

The development of ectodermal organs begins with the formation of a stratified epithelial placode that progressively invaginates into the underlying mesenchyme as the organ takes its shape. Signaling by secreted molecules is critical for epithelial morphogenesis, but how that information leads to cell rearrangement and tissue shape changes remains an open question. Using the mouse dentition as a model, we first establish that non-muscle myosin II is essential for dental epithelial invagination and show that it functions by promoting cell-cell adhesion and persistent convergent cell movements in the suprabasal layer. Shh signaling controls these processes by inducing myosin II activation via AKT. Pharmacological induction of AKT and myosin II can also rescue defects caused by the inhibition of Shh. Together, our results support a model in which the Shh signal is transmitted through myosin II to power effective cellular rearrangement for proper dental epithelial invagination. Author summary: During embryonic development, teeth, hair follicles, and glands are examples of ectodermally-derived organs that are formed from slightly thickened epithelial layers, called placodes. These placodes undergo remarkable morphological transformations to first invaginate as an epithelial bud and later morph into a more complex structure resembling the adult organ. Movement and rearrangement of epithelial cells are thought to drive tooth invagination. But there remain key knowledge gaps in our understanding of the underlying molecular mechanisms and signaling regulation that control cell movement and epithelial morphogenesis. Here, we use the developing mouse tooth as a model to show that Shh, a signaling molecule from the early tooth signaling center, plays an important role in activating the motor protein non-muscle myosin II in dental epithelial cells. Myosin II is in turn required to promote strong adhesion between cells and power dental epithelial cells to converge towards the midline of the tooth bud to drive tooth invagination. Our results thus define the in vivo function of myosin II during epithelial invagination and explain how signaling from secreted molecules can facilitate morphogenetic cell movements via myosin II. [ABSTRACT FROM AUTHOR]