On Buckling Morphogenesis

Abstract

Cell-generated mechanical forces drive many of the tissue movements and rearrangements that are required to transform simple populations of cells into the complex three-dimensional geometries of mature organs. However, mechanical forces do not need to arise from active cellular movements. Recent studies have illuminated the roles of passive forces that result from mechanical instabilities between epithelial tissues and their surroundings. These mechanical instabilities cause essentially one-dimensional epithelial tubes and two-dimensional epithelial sheets to buckle or wrinkle into complex topologies containing loops, folds, and undulations in organs as diverse as the brain, the intestine, and the lung. Here, I highlight examples of buckling and wrinkling morphogenesis, and suggest that this morphogenetic mechanism may be broadly responsible for sculpting organ form.

Fig. 1

Schematics of cortical folding in the brain, villus morphogenesis in the small intestine, and branching morphogenesis in the airways of the lung

Fig. 2

Compressive forces induce buckling of linear rods. The curvature of the buckle, k, depends in part on the thickness of the rod, t.

Fig. 3

Epithelial tissues form sheets of packed cells, similar to layered films. (a) The basal surface of epithelial sheets adheres to a basement membrane, which itself is adjacent to a loosely packed mesenchyme. (b) Thin sheets supported by a (visco)elastic foundation will form wrinkles out of the plane of the membrane when placed under compression. The wavelength of the wrinkling, λ, depends of the thickness of the sheet, its mechanical properties, and those of the foundation.

Fig. 4

Buckling/wrinkling morphogenesis of developing epithelia. (a) Looping of the vertebrate small intestine depends on the mechanical properties of the intestinal tube and the mesentery, and their relative rates of growth. With permission from Ref. [23]. (b) The luminal surface of the small intestinal epithelium morphs from smooth, to longitudinal ridges, to zigzags, to villi at the same time as the smooth muscle differentiates around the basal surface of the tube. With permission from Ref. [30]. (c) Growth of the embryonic dental epithelium under confinement might cause it to buckle into the surrounding mesenchyme. With permission from Ref. [36]. (d) The terminal end of the embryonic airway epithelium bifurcates into two daughter branches as a result of spatially patterned differentiation of airway smooth muscle. When smooth muscle differentiation is inhibited, the growing airway epithelium forms buckles instead of a bifurcation, suggesting that the smooth muscle constrains the instability. Adapted from Ref. [59].