Search

Biological tissues are composed of various cell types working cooperatively to perform their respective function within organs and the whole body. During development, embryogenesis followed by histogenesis relies on orchestrated division, death, differentiation and collective movements of cellular constituents. These cells are anchored to each other and/or the underlying substrate through adhesion complexes and they regulate force generation by active cytoskeleton remodelling. The resulting contractility related changes at the level of each single cell impact tissue architecture by triggering changes in cell shape, cell movement and remodelling of the surrounding environment. These out of equilibrium processes occur through the consumption of energy, allowing biological systems to be described by active matter physics. 'Active nematics' a subclass of active matter encompasses cytoskeleton filaments, bacterial and eukaryotic cells allowing them to be modelled as rod-like elements to which nematic liquid crystal theories can be applied. In this review, we will discuss the concept of active nematics to understand biological processes across subcellular and multicellular scales, from single cell organization to cell extrusion, collective cell movements, differentiation and morphogenesis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Collective cell migration is crucial to maintain epithelium integrity during developmental and repair processes. It requires a tight regulation of mechanical coordination between neighboring cells. This coordination embraces different features including mechanical self-propulsion of individual cells within cellular colonies and large-scale force transmission through cell-cell junctions. This review discusses how the plasticity of biomechanical interactions at cell-cell contacts could help cellular systems to perform coordinated motions and adapt to the properties of the external environment., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cell migrations are diverse. They constitutemajor morphogenetic driving forces during embryogenesis, but they contribute also to the loss of tissue homeostasis and cancer growth. Capabilities of cells to migrate as single cells or as collectives are controlled by internal and external signalling, leading to the reorganisation of their cytoskeleton as well as by the rebalancing of cell-matrix and cell-cell adhesions. Among the genes altered in numerous cancers, cadherins and growth factor receptors are of particular interest for cell migration regulation. In particular, cadherins such as N-cadherin and a class of growth factor receptors, namely FGFRs cooperate to regulate embryonic and cancer cell behaviours. In this review, we discuss on reciprocal crosstalk between N-cadherin and FGFRs during cell migration. Finally, we aim at clarifying the synergy between N-cadherin and FGFR signalling that ensure cellular reorganization during cell movements, mainly during cancer cell migration and metastasis but also during developmental processes., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

The closure of gaps is crucial to maintaining epithelium integrity during developmental and repair processes such as dorsal closure and wound healing. Depending on biochemical as well as physical properties of the microenvironment, gap closure occurs through assembly of multicellular actin-based contractile cables and/or protrusive activity of cells lining the gap. This review discusses the relative contributions of 'purse-string' and cell crawling mechanisms regulated by cell-substrate and cell-cell interactions, cellular mechanics and physical constraints from the environment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A major form of animal cell-cell adhesion results from the dynamic association of cadherin molecules, cytosolic catenins and actin microfilaments. Cadherins dynamically regulate the cytoskeleton. In turn, the actin cytoskeleton contributes to cadherin molecule oligomerization at cell contacts and to cell reshaping in response to environmental changes. Over the past two years, this evolutionarily conserved adhesion system has been intensively revisited in both its structural and functional aspects; this is illustrated by the remarkable progress in the determination of physical parameters of cadherin bonds (including force measurement) and the new insights into the role of alpha-catenin and the regulation of actin dynamics at cadherin contacts. Other recent studies uncover the important contribution of acto-myosin, microtubules and cell tension to adherens junction formation, cell differentiation and tissue reshaping/remodeling. An open challenge is now to integrate these new data with the diversity of cadherin adhesive complexes.

Vascular endothelial cadherin (VE-cadherin/cadherin5) is specifically expressed in adherens junctions of endothelial cells and exerts important functions in cell-cell adhesion as well as signal transduction. To analyze the mechanism of VE-cadherin homoassociation, the ectodomains CAD1-5 were connected by linker sequences to the N terminus of the coiled-coil domain of cartilage matrix protein (CMP). The chimera VECADCMP were expressed in mammalian cells. The trimeric coiled-coil domain leads to high intrinsic domain concentrations and multivalency promoting self-association. Ca(2+)-dependent homophilic association of VECADCMP was detected in solid phase assays and cross-linking experiments. A striking analogy to homoassociation of type I ("classical") cadherins like E, N or P-cadherin was observed when interactions in VECADCMP and between these trimeric proteins were analyzed by electron microscopy. Ca(2+)-dependent ring-like and double ring-like arrangements suggest interactions between domains 1 and 2 of the ectodomains, which may be correlated with lateral and adhesive contacts in the adhesion process. Association to complexes composed of two VECADCMP molecules was also demonstrated by chemical cross-linking. No indication for an antiparallel association of VECAD ectodomains to hexameric complexes as proposed by Legrand et al. was found. Instead the data suggest that homoassociation of VE-cadherin follows the conserved mechanism of type I cadherins.

The RAP1 subfamily of small GTPases has been involved in various differentiation programs. In skeletal muscle, several lines of evidence suggest that various small GTPases could be implicated in muscle development. This raised the question of whether the RAP1 proteins (RAP1A and/or RAP1B) could be involved in myogenesis. In the present study, we report on the regulation of RAP1 transcripts and proteins during myogenic differentiation. Northern blot analysis performed with differentiated and undifferentiated C2 myogenic cells pointed out that both genes undergo specific regulation during myogenesis in vitro since differentiation of C2 cells was accompanied by a down-regulation of RAP1B gene transcription and continuous expression of the RAP1A mRNA. In addition, immunofluorescence experiments revealed the accumulation of the RAP1 proteins in differentiated C2 cells and in primary culture of mouse myotubes. Investigation of the intracellular location of RAP1 proteins in undifferentiated and differentiated C2 cells showed that the proteins were associated with the late endocytic compartments. To verify that the build-up of RAP1 proteins had a relevance for developmental mechanisms in vivo, we studied their expression and localization at different stages of skeletal muscle development. We found that RAP1 proteins accumulated in specialized muscle cell domains undergoing important modifications during early and late myogenesis: these were the neuromuscular and myotendinous junctions, respectively. Altogether, our data indicate that RAP1 proteins are regulated during myogenic differentiation.

In this work, we investigated the distribution of the Ca(2+)-dependent cell adhesion molecule, M-cadherin, in mouse limb muscle during normal development and regeneration. Using two unrelated anti-M-cadherin peptide antibodies, we found scarce M-cadherin immunostaining during primary myogenesis (E12-E14) with no accumulation at areas of cell-cell contact. In contrast, the staining sharply increased in intensity at E16, remained high during secondary myogenesis (E16-P0) but disappeared soon after birth. During secondary myogenesis, M-cadherin was specifically accumulated at the characteristic sites of insertion of secondary myotubes in neighbouring primary myotubes. M-cadherin was also accumulated at the areas of contact between fusing secondary myoblasts and myotubes in vitro. In the adult normal and regenerating muscle, we did not detect M-cadherin accumulations at the surface of myofibres. All together, these observations suggest that M-cadherin is specifically involved in secondary myogenesis.

The expression of cytotactin, an extracellular matrix glycoprotein involved in morphogenesis and regeneration, was determined in the normal and regenerating neuromuscular system of the frog Rana temporaria. Cytotactin was expressed in adult brain and gut as two major components of Mr 190,000 and 200,000 and a minor form of higher molecular weight, but was almost undetectable in skeletal muscle extract. However, cytotactin was concentrated at the neuromuscular junctions as well as at the nodes of Ranvier. After nerve transection, cytotactin staining increased in the distal stump along the endoneurial tubes. In preparations of basal lamina sheaths of frog cutaneous pectoris muscle obtained by inducing the degeneration of both nerve and muscle fibers, cytotactin was found in dense accumulations at original synaptic sites. In order to define the role of cytotactin in axonal regeneration and muscle reinnervation, the effect of anti-cytotactin antibodies on the reinnervation of the basal lamina sheaths preparations was examined in vivo. In control preparations, regenerating nerve terminals preferentially reinnervate the original synaptic sites. In the presence of anti-cytotactin antibodies, axon regeneration occurred with normal fasciculation and branching but with altered preterminal nerve fibers pathways. Ultrastructural observations showed that synaptic basal laminae reinnervation was greatly delayed or inhibited. These results suggest that cytotactin plays a primordial role in synaptogenesis, at least during nerve regeneration and reinnervation in the adult neuromuscular system.