An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos

Abstract

Partitioning tissues into compartments that do not intermix is essential for the correct morphogenesis of animal embryos and organs. Several hypotheses have been proposed to explain compartmental cell sorting, mainly differential adhesion, but also regulation of the cytoskeleton or of cell proliferation. Nevertheless, the molecular and cellular mechanisms that keep cells apart at boundaries remain unclear. Here we demonstrate, in early Drosophila melanogaster embryos, that actomyosin-based barriers stop cells from invading neighbouring compartments. Our analysis shows that cells can transiently invade neighbouring compartments, especially when they divide, but are then pushed back into their compartment of origin. Actomyosin cytoskeletal components are enriched at compartmental boundaries, forming cable-like structures when the epidermis is mitotically active. When MyoII (non-muscle myosin II) function is inhibited, including locally at the cable by chromophore-assisted laser inactivation (CALI), in live embryos, dividing cells are no longer pushed back, leading to compartmental cell mixing. We propose that local regulation of actomyosin contractibility, rather than differential adhesion, is the primary mechanism sorting cells at compartmental boundaries.

A local difference in Hedgehog signal transduction increases mechanical cell bond tension and biases cell intercalations along the Drosophila anteroposterior compartment boundary

“…Simulations of tissue growth with two compartments furthermore suggest that such local increases in cell bond tension can prevent cell mixing between two adjacent cell populations and can account for the straight shape of compartment boundaries (Landsberg et al, 2009;Aliee et al, 2012). Consistent with these data, reducing Myosin II activity, either throughout the tissue or locally along the compartment boundary, compromises boundary shape (Major and Irvine, 2006;Landsberg et al, 2009;Monier et al, 2010;Aliee et al, 2012;Calzolari et al, 2014). Recent data suggest that local increases in cell bond tension bias cell rearrangements to maintain the straight shape of compartment boundaries (Umetsu et al, 2014).…”

“…The difference in Hedgehog signal transduction results in increased amounts of F-actin and Myosin II that have been observed along compartment boundaries and that have been termed 'actomyosin cable' Irvine, 2005, 2006;Monier et al, 2010;Calzolari et al, 2014). This term highlights the multicellular aspect of this contractile structure and might suggest that increased cell bond tension is a collective property of multiple cells along the AP boundary.…”

“…Cell junctions along compartment boundaries in Drosophila and vertebrate embryos show increased levels of F-actin and non-muscle Myosin II (Myosin II) Irvine, 2005, 2006;Landsberg et al, 2009;Monier et al, 2010;Aliee et al, 2012;Calzolari et al, 2014). It has been proposed that F-actin and Myosin II form an actomyosin cable along the compartment boundary that acts as a fence preventing the mixing of cells from adjacent compartments Irvine, 2005, 2006;Monier et al, 2010;Calzolari et al, 2014). However, whether this cable acts like an elastic string or whether mechanical tension is rather generated locally at each cell bond independently of the overall integrity of the cable remains unknown.…”

Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

“…In early Drosophila embryos, actomyosin-based contraction results in a stiffening of cell layers that physically restricts mitotic cells from intermixing with neighboring compartments. 25 Similarly, patterning of the anteroposterior axis is stabilized by the generation of actomyosin-based tension, which acts to organize and stiffen the ECM in the paraxial somatic mesoderm. 24 Tight junctions and adherens junctions mediate the forces exerted between cells to compartmentalize these developing tissues.…”

Coordinating cell polarity: heading in the right direction?

“…Later in the Drosophila embryo, as the stripes of Wingless (Wg)-expressing and Engrailed (En)-expressing cells (which define the segments of the animal) are established, mixing between these cell populations is not seen. Bénédicte Sanson (University of Cambridge, UK) described actomyosin cables that run on either side of the Wg/En cell junctions (Monier et al, 2010). These cables are under tension, forcing the border into a straight line and presumably blocking mixing.…”