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The mouse tongue possesses three types of gustatory papillae: large circumvallate papillae (CVP), foliate papillae (FOP) and fungiform papillae (FFP). Although CVP is the largest papilla and contain a high density of taste buds, little is known about CVP development. Their transition from placode to dome-shape is particularly ambiguous. Understanding this phase is crucial since dome-shaped morphology is essential for proper localization of the imminent nerve fibers and taste buds. Here, we report actomyosin-dependent apical and basal constriction of epithelial cells during dynamic epithelial folding. Furthermore, actomyosin-dependent basal constriction requires focal adhesion kinase to guide dome-shape formation. Sonic hedgehog (Shh) is closely associated with the differentiation or survival of the neurons in CVP ganglion and cytoskeletal alteration in trench epithelial cells which regulate CVP morphogenesis. Our results demonstrate the CVP morphogenesis mechanism from placode to dome-shape by actomyosin-dependent cell shape change and suggest roles that Shh may play in trench and stromal core formation during CVP development.

Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming that leads to the emergence of injury-responsive cells with fetal-like characteristics. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial cells using OSKM (Oct4, Sox2, Klf4, and c-Myc) in vivo. The OSKM-induced forced dedifferentiation showed similar molecular features of intestinal regeneration, including a transition from homeostatic cell types to injury-responsive-like cell types. These injury-responsive-like cells, sharing gene signatures of revival stem cells and atrophy-induced villus epithelial cells, actively assisted tissue regeneration following damage. In contrast to normal intestinal regeneration involving Ptgs2 induction, the OSKM promotes autonomous production of prostaglandin E2 via epithelial Ptgs1 expression. These results indicate prostaglandin synthesis is a common mechanism for intestinal regeneration but involves a different enzyme when partial reprogramming is applied to the intestinal epithelium. [ABSTRACT FROM AUTHOR]