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As organs are remodelled by morphogenetic changes and pattern formation during development, their material properties may change. To address whether and how this occurs in the mouse neural tube, we combined highly resolved mosaic analysis, biophysical modelling and perturbation experiments. We found that at early developmental stages the neuroepithelium surprisingly maintains both high junctional tension and high fluidity. This is achieved via a previously unrecognized mechanism in which interkinetic nuclear movements generate cell area dynamics that drive extensive cell rearrangements. Over time, the proliferation rate declines, effectively solidifying the tissue. Thus, unlike well-studied jamming transitions, the solidification we uncovered resembles a glass transition that depends on the dynamics of stresses generated by proliferation and differentiation. This new link between epithelial fluidity, interkinetic movements and cell cycle dynamics has implications for the precision of pattern formation and could be relevant to multiple developing tissues.

Cell division, movement and differentiation contribute to pattern formation in developing tissues. This is the case in the vertebrate neural tube where neurons differentiate in a characteristic pattern from a highly dynamic proliferating pseudostratified epithelium. To investigate how progenitor proliferation and differentiation affect cell arrangement and growth of the neural tube, we use experimental measurements to develop a mechanical model of the apical surface of the neuroepithelium that incorporates inter-kinetic nuclear movement and spatially varying rates of neuronal differentiation. Simulations predict that tissue growth and the shape of lineage-related clones of cells differ with the rate of differentiation. Growth is isotropic in regions of high differentiation, but dorsoventrally biased in regions of low differentiation. This is consistent with experimental observations. The absence of directional signalling in the simulations indicates that global mechanical constraints are sufficient to explain the observed differences in anisotropy. This provides insight into how the tissue growth rate affects cell dynamics and growth anisotropy and opens up possibilities to study the coupling between mechanics, pattern formation and growth in the neural tube.

How morphogen gradients are formed in target tissues is a key question for understanding the mechanisms of morphological patterning. Here, we review different mechanisms of morphogen gradient formation from theoretical and experimental points of view. First, a simple, comprehensive overview of the underlying biophysical principles of several mechanisms of gradient formation is provided. We then discuss the advantages and limitations of different experimental approaches to gradient formation analysis.