scholarly journals EPHecting cell contact by increasing cortical tension

2021 ◽  
Vol 220 (6) ◽  
Author(s):  
Andrea I. McClatchey

EPH/EPHRIN signaling is crucial to the segregation of cell populations during the morphogenesis of many tissues. In this issue, Kindberg et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202005216) show that EPH activation can drive both heterotypic cell repulsion and homotypic aggregation by triggering increased cortical tension.

2021 ◽  
Author(s):  
Mattias Malaguti ◽  
Rosa Portero Migueles ◽  
Jennifer Annoh ◽  
Daina Sadurska ◽  
Guillaume Blin ◽  
...  

ABSTRACTCell-cell interactions govern differentiation and cell competition in pluripotent cells during early development, but the investigation of such processes is hindered by a lack of efficient analysis tools. Here we introduce SyNPL: clonal pluripotent stem cell lines which employ optimised Synthetic Notch (SynNotch) technology to report cell-cell interactions between engineered “sender” and “receiver” cells in cultured pluripotent cells and chimaeric mouse embryos. A modular design makes it straightforward to adapt the system for programming differentiation decisions non-cell-autonomously in receiver cells in response to direct contact with sender cells. We demonstrate the utility of this system by enforcing neuronal differentiation at the boundary between two cell populations. In summary, we provide a new tool which could be used to identify cell interactions and to profile changes in gene or protein expression that result from direct cell-cell contact with defined cell populations in culture and in early embryos, and which can be adapted to generate synthetic patterning of cell fate decisions.


1974 ◽  
Vol 139 (4) ◽  
pp. 943-956 ◽  
Author(s):  
David A. Lawrence ◽  
William O. Weigle

The ability of meta-nitrobenzenediazonium fluoborate (m-NBDF)-labeled thymus and spleen (S) cells to transfer immunity to 2,4-dinitrophenyl (DNP) into irradiated syngeneic recipients was investigated. There was a significant increase in the number of anti-DNP plaque-forming cells (PFC) when m-NBDF-labeled thymus cells and normal spleen cells, or normal thymus cells and m-NBDF-labeled spleen cells were transferred, but not when both thymus- and S-cell populations were labeled and injected together into irradiated recipients. The ability of these cell populations to cooperate and enhance the in vivo immune response to DNP is discussed. The T cells seem to be actively involved in the development of this response; they participate beyond the mere role of carrying and presenting antigen to the B cells. It is suggested that cell to cell contact between T and B cells may be an important factor in the elicitation of an immune response. In addition, the cellular interaction is affected by irradiating the thymus cell preparation and the initiating interaction required for antibody synthesis probably occurs within 48 h after injecting the cell populations into the syngeneic irradiated recipients.


2020 ◽  
Author(s):  
Jana Slováková ◽  
Mateusz Sikora ◽  
Silvia Caballero-Mancebo ◽  
S.F. Gabriel Krens ◽  
Walter A. Kaufmann ◽  
...  

AbstractTension of the actomyosin cell cortex plays a key role in determining cell-cell contact growth and size. The level of cortical tension outside of the cell-cell contact, when pulling at the contact edge, scales with the total size to which a cell-cell contact can grow1,2. Here we show in zebrafish primary germ layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase, and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell-cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. Once tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell-cell contact size is limited by tension stabilizing E-cadherin-actin complexes at the contact.


1996 ◽  
Vol 5 (1) ◽  
pp. 56-61 ◽  
Author(s):  
C. Lacasse ◽  
S. Turcotte ◽  
D. Gingras ◽  
M. Rola-Pleszczynski

Co-Cultures of monocytes (MO) and endothelial cells (EC) were studied for their capacity to synergize in the production of interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM–CSF), two cytokines potentially important in vascular physiopathology. Resting monocytes produced detectable amounts of IL-6 but no GM–CSF, whereas confluent EC produced significant quantities of GM–CSF, but minimal IL-6. In co-cultures without stimuli, additive synthesis of both cytokines was observed. When EC were pretreated, however, with either PAF, TNF or both stimuli, before addition of MO, synergistic production of IL-6 was observed. In contrast, GM–CSF production was not enhanced by coculture of monocytes with activated EC. When either cell population was fixed with paraformaldehyde or killed by freeze-thawing before addition to the co-culture, cytokine levels reverted to those produced by the unaffected population alone. On the other hand, separating the two cell populations by a cell-impermeable membrane in transwell cultures did not affect the synergistic production of the cytokines. Taken together, our data suggest that EC and MO can synergize in response to stimuli by producing IL-6 and that this synergy is dependent on the integrity of both cell populations, but independent of cell-cell contact.


Author(s):  
Rahel Gerosa ◽  
Steffen Boettcher ◽  
Larisa Vladimirovna Kovtonyuk ◽  
Annika Hausmann ◽  
Wolf-Dietrich Hardt ◽  
...  

Hematopoiesis is maintained by hematopoietic stem and progenitor cells (HSPCs) that are located in the bone marrow (BM) where they are embedded within a complex supportive microenvironment, consisting of a multitude of various non-hematopoietic and hematopoietic cell types. The BM microenvironment not only regulates steady-state hematopoiesis by provision of growth factors, cytokines and cell-cell contact but is also an emerging key player during the adaptation to infectious and inflammatory insults (emergency hematopoiesis). Through a combination of gene expression analyses in prospectively isolated non-hematopoietic BM cell populations and various mouse models we have revealed that BM CXCL12-abundant reticular (CAR) cells are a major source of systemic and local BM IL-6 levels during emergency hematopoiesis following lipopolysaccharide (LPS) stimulation. Importantly, while IL-6 is dispensable during the initial phase of LPS-induced emergency hematopoiesis, it is required to sustain an adequate hematopoietic output during chronic-repetitive inflammation. Our data highlight the essential role of the non-hematopoietic BM microenvironment for the sensing and integration of pathogen-derived signals into sustained demand-adapted hematopoietic responses.


Development ◽  
2000 ◽  
Vol 127 (21) ◽  
pp. 4561-4572 ◽  
Author(s):  
T.M. Maynard ◽  
Y. Wakamatsu ◽  
J.A. Weston

We have previously shown that cultured trunk neural crest cell populations irreversibly lose neurogenic ability when dispersal is prevented or delayed, while the ability to produce other crest derivatives is retained (Vogel, K. S. and Weston, J. A. (1988) Neuron 1, 569–577). Here, we show that when crest cells are prevented from dispersing, cell death is increased and neurogenesis is decreased in the population, as a result of high cell density. Control experiments to characterize the effects of high cell density on environmental conditions in culture suggest that reduced neurogenesis is the result of cell-cell interactions and not changes (conditioning or depletion) of the culture medium. Additionally, we show that the caspase inhibitor zVAD-fmk, which blocks developmentally regulated cell death, rescues the neurogenic ability of high density cultures, without any apparent effect on normal, low-density cultures. We conclude, therefore, that increased cell interaction at high cell densities results in the selective death of neurogenic precursors in the nascent crest population. Furthermore, we show that neurogenic cells in cultured crest cell populations that have dispersed immediately are not susceptible to contact-mediated death, even if they are subsequently cultured at high cell density. Since most early migrating avian crest cells express Notch1, and a subset expresses Delta1 (Wakamatsu, Y., Maynard, T. M. and Weston, J. A. (2000) Development 127, 2811–2821), we tested the possibility that the effects of cell contact were mediated by components of a Notch signaling pathway. We found that neurogenic precursors are eliminated when crest cells are co-cultured with exogenous Delta1-expressing cells immediately after they segregate from the neural tube, although not after they have previously dispersed. We conclude that early and prolonged cell interactions, mediated at least in part by Notch signaling, can regulate the survival of neurogenic cells within the nascent crest population. We suggest that a transient episode of cell contact-mediated death of neurogenic cells may serve to eliminate fate-restricted neurogenic cells that fail to disperse promptly in vivo.


Author(s):  
David G. Wilkinson

The segregation of distinct cell populations to form sharp boundaries is crucial for stabilising tissue organisation, for example during hindbrain segmentation in craniofacial development. Two types of mechanisms have been found to underlie cell segregation: differential adhesion mediated by cadherins, and Eph receptor and ephrin signalling at the heterotypic interface which regulates cell adhesion, cortical tension and repulsion. An interplay occurs between these mechanisms since cadherins have been found to contribute to Eph-ephrin-mediated cell segregation. This may reflect that Eph receptor activation acts through multiple pathways to decrease cadherin-mediated adhesion which can drive cell segregation. However, Eph receptors mainly drive cell segregation through increased heterotypic tension or repulsion. Cadherins contribute to cell segregation by antagonising homotypic tension within each cell population. This suppression of homotypic tension increases the difference with heterotypic tension triggered by Eph receptor activation, and it is this differential tension that drives cell segregation and border sharpening.


2011 ◽  
Vol 8 (63) ◽  
pp. 1462-1471 ◽  
Author(s):  
M. J. P. Biggs ◽  
M. C. Milone ◽  
L. C. Santos ◽  
A. Gondarenko ◽  
S. J. Wind

T-cell activation via antigen presentation is associated with the formation of a macromolecular membrane assembly termed the immunological synapse (IS). The genesis of the IS and the onset of juxtacrine signalling is characterized by the formation of cell membrane microclusters and the organization of such into segregated microdomains. A central zone rich in T-cell receptor (TCR)–major histocompatibility complex microclusters termed the central supramolecular activation cluster (cSMAC) forms the bullseye of this structure, while the cellular interface surrounding the cSMAC is characterized by regions enriched in adhesion and co-stimulatory molecules. In vitro , the study of dynamic TCR microcluster coalescence and IS genesis in T-cell populations is hampered by cell migration within the culture system and resolution constraints resulting from lateral cell–cell contact. Here, we detail a novel system describing the fabrication of micropit arrays designed to sequester single T-cell–antigen presenting cell (APC) conjugates and promote IS formation in the horizontal imaging plane for high-resolution studies of microcluster dynamics. We subsequently use this system to describe the formation of the cSMAC in T-cell populations and to investigate the morphology of the interfacial APC membrane.


Author(s):  
T. G. Sarphie ◽  
C. R. Comer ◽  
D. J. Allen

Previous ultrastructural studies have characterized surface morphology during norma cell cycles in an attempt to associate specific changes with specific metabolic processes occurring within the cell. It is now known that during the synthetic ("S") stage of the cycle, when DNA and other nuclear components are synthesized, a cel undergoes a doubling in volume that is accompanied by an increase in surface area whereby its plasma membrane is elaborated into a variety of processes originally referred to as microvilli. In addition, changes in the normal distribution of glycoproteins and polysaccharides derived from cell surfaces have been reported as depreciating after cellular transformation by RNA or DNA viruses and have been associated with the state of growth, irregardless of the rate of proliferation. More specifically, examination of the surface carbohydrate content of synchronous KB cells were shown to be markedly reduced as the cell population approached division Comparison of hamster kidney fibroblasts inhibited by vinblastin sulfate while in metaphase with those not in metaphase demonstrated an appreciable decrease in surface carbohydrate in the former.


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