Tissue boundary formation in the early vertebrate embryo involves cycles of cell attachment and detachment at the boundary, and cell contact-dependent signaling by membrane-bound EphB receptors and ephrinB ligands.

Morphogenetic processes often involve the rapid rearrangement of cells held together by mutual adhesion. The dynamic nature of this adhesion endows tissues with liquid-like properties, such that largescale shape changes appear as tissue flows. Generally, the resistance to flow (tissue viscosity) is expected to depend on the cohesion of a tissue (how strongly its cells adhere to each other), but the exact relationship between these parameters is not known. Here, we analyse the link between cohesion and viscosity to uncover basic mechanical principles of cell rearrangement. We show that for vertebrate and invertebrate tissues, viscosity varies in proportion to cohesion over a 200-fold range of values. We demonstrate that this proportionality is predicted by a cell-based model of tissue viscosity. To do so, we analyse cell adhesion in Xenopus embryonic tissues and determine a number of parameters, including tissue surface tension (as a measure of cohesion), cell contact fluctuation and cortical tension. In the tissues studied, the ratio of surface tension to viscosity, which has the dimension of a velocity, is 1.8 µm/min. This characteristic velocity reflects the rate of cell-cell boundary contraction during rearrangement, and sets a limit to rearrangement rates. Moreover, we propose that, in these tissues, cell movement is maximally efficient. Our approach to cell rearrangement mechanics links adhesion to the resistance of a tissue to plastic deformation, identifies the characteristic velocity of the process, and provides a basis for the comparison of tissues with mechanical properties that may vary by orders of magnitude.

Epithelia are planar tissues that undergo major morphogenetic movements during development. These movements must work in the context of the mechanical properties of epithelia. Surprisingly little is known about these mechanical properties at the time and length scales of morphogenetic processes. We show that at a time scale of hours, Xenopus gastrula ectodermal epithelium mimics an elastic solid when stretched isometrically; strikingly, its area increases twofold in the embryo by such pseudoelastic expansion. At the same time, the basal side of the epithelium behaves like a liquid and exhibits tissue surface tension that minimizes its exposed area. We measure epithelial stiffness (∼1 mN/m), surface tension (∼0.6 mJ/m 2 ), and epithelium-mesenchyme interfacial tensions and relate these to the folding of isolated epithelia and to the extent of epithelial spreading on various tissues. We propose that pseudoelasticity and tissue surface tension are main determinants of epithelial behavior at the scale of morphogenetic processes.

␤-Catenin-independent Wnt signaling pathways have been implicated in the regulation of planar cell polarity (PCP) and convergent extension (CE) cell movements. Prickle, one of the core proteins of these pathways, is known to asymmetrically localize proximally at the adherens junction of Drosophila melanogaster wing cells and to locally accumulate within plasma membrane subdomains in cells undergoing CE movements during vertebrate development. Using mass spectrometry, we have identified the Ste20 kinase Mink1 as a Prickle-associated protein and found that they genetically interact during the establishment of PCP in the Drosophila eye and CE in Xenopus laevis embryos. We show that Mink1 phosphorylates Prickle on a conserved threonine residue and regulates its Rab5-dependent endosomal trafficking, a process required for the localized plasma membrane accumulation and function of Prickle. Mink1 also was found to be important for the clustering of Vangl within plasma membrane puncta. Our results provide a link between Mink and the Vangl-Prickle complex and highlight the importance of Prickle phosphorylation and endosomal trafficking for its function during Wnt-PCP signaling. P lanar cell polarity (PCP), which is orthogonal to the cell apicobasal axis, is important to coordinate cellular orientation at the tissue level (15,41,56,57,63). The stereotypical orientation of the hairs at the distal tip of Drosophila melanogaster wing cells and the organization of the photoreceptor cells in the fly compound eye are two particularly striking manifestations of PCP that have been exploited as model systems for its study. Genetic screens have identified a core set of proteins that are important for the establishment and maintenance of PCP. These proteins include Frizzled (Fz) (1, 55), Flamingo (Fmi) (53), Van Gogh (Vangl) (50, 61), Dishevelled (Dsh) (39), Diego (16), and Prickle (Pk) (18). The underlying molecular mechanisms of how the core PCP proteins regulate cell polarity are poorly understood. At the cellular level, the asymmetric localization of the PCP core proteins on the apical cortex is thought to be key for PCP establishment (45). In the Drosophila wing, the seven-transmembrane protein Fz along with the cytosolic proteins Dsh and Diego are distally localized, whereas the four-transmembrane protein Vangl and the membrane-associated protein Pk are proximally localized. The asymmetric localization of these core proteins is thought to result from intracellular feedback interactions between proximal Vangl-Pk and distal Fz-Dsh protein complexes. One emerging mechanism that has been proposed to control the asymmetric distribution of PCP proteins involves the polarized control of membrane-trafficking events. The microtubule-dependent polarized transport of Fmi and Fz (42,46), as well as the regulation of Fz and Fmi endocytosis (32,46,47), have been shown to play key roles in their localized accumulation on the cortex. Furthermore, it has been demonstrated recently that the cytoplasmic PCP core proteins Dsh, Pk, and Dgo are req...

In Xenopus and zebrafish gastrulae, PAPC attenuates planar cell polarity signaling and controls formation of an adhesive, yet flexible, contact at the ectoderm–mesoderm boundary.