Anisotropic Cell Shape and Motion Coordinate Hindbrain Neuropore Morphogenesis.

Neural tube closure is a critical morphogenetic process in vertebrate development, and failure to close cranial regions such as the hindbrain neuropore (HNP) leads to severe congenital malformations. While mechanical forces like actomyosin purse-string contraction and directional cell crawling have been implicated in driving HNP closure, how these forces organize local cell shape and motion to produce large-scale tissue remodeling remains poorly understood. Using live and fixed imaging of mouse embryos combined with cell-based biophysical modeling, we show that these force-generating mechanisms are insufficient to explain the robust patterns of cell elongation and nematic alignment observed at the HNP border.

Tension Remodeling Regulates Topological Transitions in Epithelial Tissues.

Cell neighbor exchanges play a critical role in regulating tissue fluidity during epithelial morphogenesis and repair. , these neighbor exchanges are often hindered by the formation of transiently stable fourfold vertices, which can develop into complex multicellular rosettes where five or more cell junctions meet. Despite their importance, the mechanical origins of multicellular rosettes have remained elusive, and current cellular models lack the ability to explain their formation and maintenance.

Mechanical control of cell proliferation patterns in growing epithelial monolayers.

Cell proliferation plays a crucial role in regulating tissue homeostasis and development. However, our understanding of how cell proliferation is controlled in densely packed tissues is limited. Here we develop a computational framework to predict the patterns of cell proliferation in growing epithelial tissues, connecting single-cell behaviors and cell-cell interactions to tissue-level growth.

Excitable dynamics driven by mechanical feedback in biological tissues.

Pulsatory activity patterns, driven by mechanochemical feedback, are prevalent in many biological systems. However, the role of cellular mechanics and geometry in the propagation of pulsatory signals remains poorly understood. Here we present a theoretical framework to elucidate the mechanical origin and regulation of pulsatile activity patterns within excitable multicellular tissues.

Continuum description of confluent tissues with spatial heterogeneous activity.

A continuum description is built to characterize the stationary and transient deformations of confluent tissues subject to heterogeneous activities. By defining a coarse-grained texture matrix field to represent the shape and size of cells, we derive the coarse-grained stress tensor for the vertex model. Activity in the tissue takes the form of inhomogeneous apical contractions, which can be modeled as reductions of the vertex model reference areas or perimeters representing activity in the medial and perimeter regions of the cells, respectively.

Mechanical control of cell proliferation patterns in growing tissues.

Cell proliferation plays a crucial role in regulating tissue homeostasis and development. However, our understanding of how cell proliferation is controlled in densely packed tissues is limited. Here we develop a computational framework to predict the patterns of cell proliferation in growing tissues, connecting single-cell behaviors and cell-cell interactions to tissue-level growth.

Geometrical characterization of active contraction pulses in epithelial cells using the two-dimensional vertex model.

Several models have been proposed to describe the dynamics of epithelial tissues undergoing morphogenetic changes driven by apical constriction pulses, which differ in where the constriction is applied, either at the perimeter or in the medial regions. To help discriminate between these models, we analyse the impact of where constriction is applied on the final geometry of the active contracted cell, using the two-dimensional vertex model. We find that medial activity, characterized by a reduction in the reference area, generates anisotropic cell shapes, whereas isotropic cell shapes are produced when the reference perimeter is reduced.

Vertex model instabilities for tissues subject to cellular activity or applied stresses.

The vertex model is widely used to describe the dynamics of epithelial tissues, because of its simplicity and versatility and the direct inclusion of biophysical parameters. Here, it is shown that quite generally, when cells modify their equilibrium perimeter due to their activity, or the tissue is subject to external stresses, the tissue becomes unstable with deformations that couple pure shear or deviatoric modes, with rotation and expansion modes. For short times, these instabilities deform cells, increasing their ellipticity, while at longer times cells become nonconvex, indicating that the vertex model ceases to be a valid description for tissues under these conditions.