Cells: shaping tissues and organs

Apical constriction During several morphogenetic developmental processes, epithelial sheets contract some of their cells to cause invaginations or bending. To do this, epithelial cells constrict apically located actin and myosin while lengthening the basolateral axis in a process called apical constriction. Frank Mason (Martin Laboratory, Massachusetts Institute of Technology) showed that RhoA signaling is polarized to the center of the apical surface and that this stabilizes actomyosin structures spanning the apex. Bing He (Wieschaus Laboratory, Princeton University) found that these contractile forces also cause the cell to lengthen by an unexpected force—viscous flow. Apical constriction drives the viscous cytoplasm, as visualized by injected beads, to stream along the surface of the embryo and converge toward the ventral midline, where it forms an inward flow perpendicular to the surface that leads to cell lengthening. In this process, cell membranes were found to passively move with the ambient cytoplasm without offering appreciable driving force or resistance. Matrix shaping of cells, nuclei, and tissue Two talks investigated how the matrix can impact cell behavior. Zev Gartner (University of California, San Francisco) discussed how epithelia with heterogeneous cell–cell interactions could self-organize into a bilayer depending on cell identity only if embedded within a matrix that programs this layering. If these same cells are embedded in inert agarose gels, they cannot segregate properly into two layers. This is because the matrix only binds the outer myoepithelial cells, which in turn bind the nonadhesive inner luminal epithelial cells, thereby layering tissues from the outside-in. Alternatively, density of the matrix can affect the shape of the cell nucleus by altering its lamin A content. Joe Swift (Discher Laboratory, University of Pennsylvania) showed that when cells are plated on a stiffer matrix, lamin A, but not lamin B, increases and polymerizes at the nuclear envelope. Increased lamin A at the nuclear envelope could act as a shock absorber for nuclei as cells become compressed in stiff tissue. Diseases such as muscular dystrophy have point mutations in the stress-sensitive regions of lamin A that could affect cell function in stiff tissue. Moreover, low or high levels of lamin A increase differentiation of stem cells into fat or bone, respectively, suggesting lamin A’s importance in regulating nuclear structure and function.