Cellular mechanisms of reverse epithelial curvature in tissue morphogenesis

Abstract

Epithelial bending plays an essential role during the multiple stages of organogenesis and can be classified into two types: invagination and evagination. The early stages of invaginating and evaginating organs are often depicted as simple concave and convex curves respectively, but in fact majority of the epithelial organs develop through a more complex pattern of curvature: concave flanked by convex and vice versa respectively. At the cellular level, this is far from a geometrical truism: locally cells must passively adapt to, or actively create such an epithelial structure that is typically composed of opposite and connected folds that form at least one s-shaped curve that we here, based on its appearance, term as “reverse curves.” In recent years, invagination and evagination have been studied in increasing cellular detail. A diversity of mechanisms, including apical/basal constriction, vertical telescoping and extrinsic factors, all orchestrate epithelial bending to give different organs their final shape. However, how cells behave collectively to generate reverse curves remains less well-known. Here we review experimental models that characteristically form reverse curves during organogenesis. These include the circumvallate papillae in the tongue, crypt–villus structure in the intestine, and early tooth germ and describe how, in each case, reverse curves form to connect an invaginated or evaginated placode or opposite epithelial folds. Furthermore, by referring to the multicellular system that occur in the invagination and evagination, we attempt to provide a summary of mechanisms thought to be involved in reverse curvature consisting of apical/basal constriction, and extrinsic factors. Finally, we describe the emerging techniques in the current investigations, such as organoid culture, computational modelling and live imaging technologies that have been utilized to improve our understanding of the cellular mechanisms in early tissue morphogenesis.

Whole Tissue Imaging of Cellular Boundaries at Sub-Micron Resolutions for Automatic Cell Segmentation: Applications in Epithelial Bending of Ectodermal Appendages

“…To obtain cellular information within the tissue interior, we produced virtual sections through the segmented and cell property-labeled images to obtain 2-D snapshots of 3-D cellular morphology information about cells from a particular tissue region and view (Figure 6). Epithelial morphogenic processes, fundamentally rely on the bending of epithelial sheets that, in simple terms, can occur by two different modes: invagination into the underlying tissue; and evagination outwards from the epithelial surface ( 17 ), however, the mechanisms by which epithelial bending direction is not well understood. Using the catshark mandibular dental lamina (Figure 6i,ii) and tail-tip dermal denticles (Figure 6iii, iv) as examples, we compared the cellular properties of both invaginating (dental lamina) and evaginating (dermal denticles) tissue structures.…”

Local Mechanical Modulation-Driven Evagination in Invaginated Epithelia

“…To date, scant attention has been directed toward the simultaneous occurrence of two contrary curves, despite their appearance being essential for the progression of many epithelial organs to more advanced stages of morphogenesis. While much is known about the underlying genetic regulation of these events, a global understanding of the physical mechanisms orchestrating this sophisticated morphology remains elusive.…”