Past exam of the zoology course of the University of Cambridge / 2025 / Paper zl6 / 6 / b / Solution

Mechanics shapes tissues by generating active forces, directing rearrangements and converting constrained growth into deformation. Three experimentally distinct examples are folding of the fly ventral epithelium, elongation of the fly germband and formation of chick intestinal villi. They respectively emphasize changes in cell shape, changes in cell neighbours and a growth-driven instability. In each case, a satisfactory explanation needs both a force-generating process and the material or boundary conditions that convert it into a particular shape.

First, apical constriction drives Drosophila ventral furrow formation. Ventral cells accumulate a contractile actomyosin network near their apical surfaces. Reducing apical area while retaining tissue continuity changes cell geometry and contributes to inward bending of the epithelial sheet. This is not adequately described as uniform contraction of a permanent circumferential belt. Time-resolved imaging showed pulses of medioapical myosin II accumulation associated with discrete contractions, and stabilization between pulses permits net constriction. Regulation by Snail and Twist helps coordinate contraction and the retention of the resulting shape.^[ref]

The force must be transmitted to neighbouring cells through adherens junctions; a detached contracting cortex can deform internally without folding a coherent sheet. Geometry is therefore a collective property. A useful causal test compares acute inhibition of myosin activation with perturbation of junctional coupling, scoring apical area, contraction pulses, cell length and tissue curvature separately. laser ablation can reveal the direction of tissue load, and localized activation of contractility can test whether the site of force generation predicts bending. Recoil velocity alone is not tension: in an overdamped approximation $v_0\sim T/\zeta$, where $T$ is released tension and $\zeta$ an effective resistance. Comparing recoil between conditions requires considering possible changes in resistance as well as load. External pressure, basal constraints and neighbouring tissue movement also influence invagination, so apical contraction need not be sufficient under every boundary condition.

Second, Drosophila germband extension changes tissue aspect ratio through oriented cell intercalation. Selected cell junctions shrink, cells briefly share a vertex or multicellular rosette, and new junctions appear in the complementary orientation. Repeated local neighbour exchanges extend the tissue along one axis while narrowing it along the other. myosin II is enriched at the shrinking interfaces, and interfering with its activity disrupts polarized junction remodelling. This supplies a mechanism for convergent extension without requiring that every cell grow longer or that an increased number of divisions provide the extension.^[ref]

Here the crucial distinction is between active rearrangement and passive stretching. Track all vertices and neighbours in a patch and decompose tissue deformation into cell-shape change, neighbour exchange and cell-number change. A tissue can lengthen while individual cells remain similar in shape if topology changes; alternatively, pulling from a neighbouring tissue can elongate cells without local intercalation supplying the force. Test whether local myosin inhibition suppresses the junction transitions before global tissue movement is lost, and compare spatial patterns of load by laser ablation. Rescue must restore directional transitions as well as the final length. planar cell polarity provides the orientation, and junctional adhesion permits force transmission while contacts are remodelled. Thus mechanics can translate a molecular anisotropy into coordinated movement of an epithelial sheet.

Third, chick intestinal villi illustrate differential growth constrained by surrounding layers. The growing inner tissues are enclosed by sequentially differentiating smooth muscle layers. Mechanical constraints drive a progression from longitudinal ridges through zigzags toward a villous surface. The important process is not simply muscle contraction pushing each villus into place: the muscle acts as a restricting layer against which continued tissue growth builds compressive stress. In the primary experiments, blocking muscle differentiation prevented the expected folding, while an artificial constraining silk tube could restore folding in the inhibited tissue. This rescue is particularly informative because it replaces a living layer's mechanical contribution without restoring all its possible signals.^[ref]

The physical principle is a buckling instability: a sufficiently compressed growing layer can lower its mechanical cost by bending. The wavelength and mode depend on geometry, thickness and stiffness, so equal amounts of growth need not yield equal shapes in different environments. An ideal thin-plate model has bending rigidity $B=E{h}^3/[12(1-{\nu }^2)]$, with Young's modulus $E$, thickness $h$ and Poisson's ratio $\nu$. It predicts strong thickness sensitivity of resistance to bending, but this formula alone does not compute the wavelength of a living multilayer gut. That requires measured geometry, growth and an appropriate constitutive model. Compare proliferation, muscle differentiation, material properties and folding after each perturbation to distinguish mechanical confinement from secondary effects on growth.

The chick example should not be imposed unmodified on mouse villus development, where mesenchymal cluster patterning precedes the corresponding epithelial deformation. Nor is any of the three mechanisms independent of chemical signalling: signals position contractility, specify muscle and regulate adhesion, while mechanical deformation changes the subsequent signalling environment. Their distinct causal signatures are nonetheless clear. A contractile apical network folds a coupled sheet; anisotropic junctional tension changes neighbours and tissue aspect ratio; constrained growth generates an instability whose form depends on material properties. Testing these signatures through timed perturbation and mechanical rescue explains organ shape more precisely than simply observing that a cytoskeletal protein is required.