Apical constriction: themes and variations on a cellular mechanism driving morphogenesis

Abstract

Apical constriction is a cell shape change that promotes tissue remodeling in a variety of homeostatic and developmental contexts, including gastrulation in many organisms and neural tube formation in vertebrates. In recent years, progress has been made towards understanding how the distinct cell biological processes that together drive apical constriction are coordinated. These processes include the contraction of actin-myosin networks, which generates force, and the attachment of actin networks to cell-cell junctions, which allows forces to be transmitted between cells. Different cell types regulate contractility and adhesion in unique ways, resulting in apical constriction with varying dynamics and subcellular organizations, as well as a variety of resulting tissue shape changes. Understanding both the common themes and the variations in apical constriction mechanisms promises to provide insight into the mechanics that underlie tissue morphogenesis.

Keywords: Actin; Adhesion; Apical; Cadherin; Constriction; Myosin.

Fig. 1.

Functions and examples of apical constriction. (A-C) Apical constriction functions in various contexts including: (A) tissue folding and tube formation, seen in examples of gastrulation and vertebrate neurulation; (B) ingression of individual cells and epithelial-to-mesenchymal (EMT) transitions, as occur in other examples of gastrulation and in tissue homeostasis; and (C) healing and sealing of embryonic tissues in response to wound healing. The cell and tissue movements (green arrows) that occur as specific cells undergo constriction of their apical sides (orange) are indicated in each context. Wound healing can involve apical constriction of an underlying layer of cells, or of a ring of cells (dashed line; just two such cells of the ring are drawn) at the periphery of a wound.

Fig. 2.

Mechanisms of apical constriction. Key components involved in apical constriction include F-actin (red) and myosin (orange), which form contractile networks. Actin-myosin networks can be organized into contractile bundles/fibers or can be organized into a more loosely organized two-dimensional network that underlies the plasma membrane, called the apical cortex. Shrinkage of the apical cortex (green arrows) is driven by actin-myosin contractions. Apical adherens junctions (AJs, gray) link cells, allowing apical actin-myosin contractions to drive tissue shape changes. In this example, only the apical actin cortex is shown.

Fig. 3.

Apical constriction by cortical actin-myosin flows. (A) Apical constriction in C. elegans gastrulation. Membranes, which are marked with an mCherry (red) membrane marker, were imaged using Bessel beam super-resolution structured illumination microscopy (Gao et al., 2012). Images courtesy of C. Higgins and L. Gao. Two stages (early and late) are shown to highlight the internalization of the two endodermal precursor cells, the exposed apical domains of which are indicated (yellow dashed lines) at each stage. Below, optical sections of the same embryos at the same stages are shown. Endodermal precursor cells are marked (asterisks), and the direction of their internalization is indicated (green arrow). (B) A C. elegans embryo (∼50 µm long) in which the apical constriction of endoderm precursor cells has begun. The embryo expresses GFP-tagged myosin (green) and an mCherry-tagged plasma membrane marker (red). This spinning disk confocal image shows the large number of myosin foci visible in the apical cortex of endoderm precursor cells (asterisks; apical domain outlined by yellow dashed line). Image courtesy of C. Higgins.

Fig. 4.

Variations in the spatial localization of actin-myosin structures during apical constriction. (A) Schematic illustrating the location of circumferential actin-myosin networks and medioapical actin-myosin networks (both illustrated in red). (B) A conserved pathway, involving PDZ-RhoGEF, RhoA, ROCK and Diaphanous (Dia), regulates myosin activation and F-actin assembly in Drosophila mesoderm cells and the chicken neural tube. (C) Cross-sections (top) and apical surface (bottom) views of Drosophila mesoderm cells during gastrulation (left) and of the chick neural tube (right). Myosin (green) is preferentially in the medioapical domain in the Drosophila presumptive mesoderm cells, but is preferentially at junctions during chick neurulation. Asterisk marks the site of invagination, where mesoderm precursor cells are undergoing apical constriction. In the apical views, a single cell is outlined (yellow dotted line). Axes are also marked: apical-basal (ap-ba), medial-lateral (M-L) and anterior-posterior (A-P). Drosophila cross-section courtesy of C. Vasquez and neural tube images courtesy of M. Takeichi (Nishimura et al., 2012). (D) Key components of the RhoA pathway exhibit different spatial organizations during Drosophila gastrulation and vertebrate neurulation. During Drosophila gastrulation, mesoderm cells exhibit a radial cell polarity (RCP) in which RhoA (purple) and its effector ROCK (pink) are present in a medioapical focus. RhoA is also present at junctions. Dia (green) is present at junctions and throughout the apical cortex. During chick neurulation, PDZ-RhoGEF (purple) and ROCK (pink) are localized at junctions and exhibit planar cell polarity (PCP). In left-hand diagram, green arrows indicate constriction.

Fig. 5.

Evidence for dynamic regulation of connections between the actin-myosin cortex and apical junctions. At the onset of gastrulation in C. elegans and Drosophila (top), myosin (orange) and the associated network initially flows centripetally without moving apical junctions in concert and, hence, without causing shrinking of the apical domain. Centripetal actin-myosin contraction is represented by green arrows. Later (bottom), cortical actin-myosin flow moves more in concert with apical junctions (green arrows), which converge, shrinking the apical surface.

Fig. 6.

Organization of contractile tissues during Drosophila dorsal closure. (A) Closure of the dorsal ‘hole’ in the Drosophila epidermis is driven by contraction of amnioserosa (AS) cells that occupy this hole (red arrows) and by contraction of a supracellular actin-myosin cable present at the leading edge of the epidermis (green arrows). (B) Morphology of the apical domain and of apical myosin in AS cells and the epidermis. AS cells have large apical domains that exhibit pulsed accumulations of myosin (red arrowheads, myosin accumulation in different AS cells). By contrast, epidermis cells exhibit myosin accumulation at the junctional interface with the AS cells (green arrowhead). Images represent different embryos. Images courtesy of T. Harris.

Fig. 7.

Evidence for actin-myosin-dependent ratcheting of pulsed contractions. Pulsed contractions can occur without stabilization of the constricted apical surface area between pulses, resulting in cell shape fluctuations (left). These unratcheted constrictions have been observed in Drosophila amnioserosa cells before the onset of dorsal closure and in Drosophila presumptive mesoderm cells mutant for twist. Alternatively, decreases in apical surface area that result from contractile pulses can be stabilized, resulting in what sometimes resembles an incremental or ratchet-like decrease in apical area (right). This behavior is observed for wild-type presumptive mesoderm cells during Drosophila gastrulation and in amnioserosa cells during dorsal closure. In both these cases, both myosin and F-actin persist to a greater degree between pulses (right), which possibly prevents relaxation, resulting in a net reduction in apical surface area. Green arrows indicate shrinkage or expansion of apical domains.