scholarly journals Asymmetry at cell-cell interfaces direct cell sorting, boundary formation, and tissue morphogenesis

2017 ◽  
Vol 358 (1) ◽  
pp. 58-64 ◽  
Author(s):  
Rosa Ventrella ◽  
Nihal Kaplan ◽  
Spiro Getsios
Keyword(s):  
Cell Sorting ◽  
Tissue Morphogenesis ◽  
Boundary Formation ◽  
Direct Cell ◽  
Cell Cell

Abstract 15392: Inflammation and Ischemic Heart Failure: Monocyte-Mediated Cardiac Fibroblast Activation and Matrix Remodeling Through a Direct Cell-Cell Contact Mechanism

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Holly E Mewhort ◽  
Brodie D Lipon ◽  
Daniyil A Svystonyuk ◽  
David G Guzzardi ◽  
Paul W Fedak
Keyword(s):  
Peripheral Blood ◽  
Cardiac Fibroblast ◽  
Cell Contact ◽  
Β1 Integrin ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Fibroblast Activation ◽  
Direct Cell ◽  
Tgf Β1 ◽  
Cell Cell

BACKGROUND: Following myocardial infarction (MI), activated cardiac myofibroblasts facilitate extracellular matrix (ECM) remodeling to prevent mechanical complications. However, prolonged myofibroblast activity leads to dysregulation of the ECM, maladaptive remodeling, fibrosis and heart failure (HF). Chronic inflammation is believed to drive persistent myofibroblast activity, however, the mechanisms are unclear. In this study, we explored the effects of peripheral blood monocytes on human cardiac fibroblast activation in a 3D ECM microenvironment. METHODS/RESULTS: Human cardiac fibroblasts isolated from surgical human heart biopsies were seeded into 3D collagen matrices. Peripheral blood monocytes isolated from healthy human donors were co-cultured with fibroblasts. Monocytes increased fibroblast activation measured by collagen ECM contraction (17.9±11.1% increase; p<0.01) and resulted in local ECM remodeling observed by confocal microscopy. Under co-culture conditions that prevent cell-cell contact but allow interaction via paracrine factors, monocytes had minimal effects on fibroblast activation (6.4±7.0 vs.17.9±11.1% increase, respectively; p<0.01). Multiplex analysis of the co-culture media revealed an increase in the paracrine factors Transforming Growth Factor-beta 1 (TGF-β1) and Matrix Metalloproteinase 9 when monocytes and fibroblasts were cultured under cell-cell contact conditions (162.2±11.7pg/mL and 17.5±0.5ng/mL, respectively, vs. 21.8±5.7pg/mL and 4.9 ±0.4ng/mL; p<0.001). TGF-β1 blockade abolished monocyte induced cardiac fibroblast activation, as did β1-integrin. These data suggest direct cell-cell interaction between monocytes and cardiac fibroblasts through β1-integrin results in TGF-β1 release facilitating fibroblast activation and matrix remodeling. CONCLUSION: For the first time, we demonstrate that peripheral blood monocytes stimulate human cardiac fibroblast activation through a mechanism involving TGF-β1 release as a consequence of direct cell-cell interaction through β1-integrin. These data implicate inflammation as a driver of cardiac fibrosis post-MI, highlighting potential novel therapeutic targets for the treatment of ischemic HF.

Eph signalling functions downstream of Val to regulate cell sorting and boundary formation in the caudal hindbrain

Development ◽  
2001 ◽  
Vol 128 (4) ◽  
pp. 571-580 ◽  
Author(s):  
J. Cooke ◽  
C. Moens ◽  
L. Roth ◽  
L. Durbin ◽  
K. Shiomi ◽  
...  
Keyword(s):  
Cell Sorting ◽  
Tyrosine Kinases ◽  
Bzip Transcription Factor ◽  
Boundary Formation ◽  
Spatial Regulation ◽  
Genetic Mosaic ◽  
Mosaic Approach ◽  
Mediate Cell ◽  
Neural Crest Migration ◽  
Mutant Cells

Rhombomeres are segmental units of the developing vertebrate hindbrain that underlie the reiterated organisation of cranial neural crest migration and neuronal differentiation. valentino (val), a zebrafish homologue of the mouse bzip transcription factor-encoding gene, kreisler, is required for segment boundary formation caudal to rhombomere 4 (r4). val is normally expressed in r5/6 and is required for cells to contribute to this region. In val(−) mutants, rX, a region one rhombomere in length and of mixed identity, lies between r4 and r7. While a number of genes involved in establishing rhombomeric identity are known, it is still largely unclear how segmental integrity is established and boundaries are formed. Members of the Eph family of receptor tyrosine kinases and their ligands, the ephrins, are candidates for functioning in rhombomere boundary formation. Indeed, expression of the receptor ephB4a coincides with val in r5/6, whilst ephrin-B2a, which encodes a ligand for EphB4a, is expressed in r4 and r7, complementary to the domain of val expression. Here we show that in val(−) embryos, ephB4a expression is downregulated and ephrin-B2a expression is upregulated between r4 and r7, indicating that Val is normally required to establish the mutually exclusive expression domains of these two genes. We show that juxtaposition of ephB4a-expressing cells and ephrin-B2a-expressing cells in the hindbrain leads to boundary formation. Loss of the normal spatial regulation of eph/ephrin expression in val mutants correlates not only with absence of boundaries but also with the inability of mutant cells to contribute to wild-type r5/6. Using a genetic mosaic approach, we show that spatially inappropriate Eph signalling underlies the repulsion of val(−) cells from r5/6. We propose that Val controls eph expression and that interactions between EphB4a and Ephrin-B2a mediate cell sorting and boundary formation in the segmenting caudal hindbrain.

Stiffness as an Effector of Lung Branching Morphogenesis

2012 ◽  
Author(s):  
Kelly C. Clause ◽  
Tatiana Segura ◽  
Thomas H. Barker
Keyword(s):  
Cell Fate ◽  
In Vitro Study ◽  
Branching Morphogenesis ◽  
Substrate Stiffness ◽  
Tissue Morphogenesis ◽  
Mechanical Stiffness ◽  
Physical Cues ◽  
Direct Cell ◽  
Cleft Formation

Growing evidence suggests that physical microenvironments and mechanical stresses direct cell fate in developing tissues. However, how these physical properties affect morphogenesis remains unknown. We show here that ECM mechanical properties, i.e. stiffness, reproduced by using hydrogel, guide tissue morphogenesis in the developing lung bud. In particular, decreasing substrate stiffness in cultured lung buds resulted in an inhibition of appropriate cleft formation and a resulting enlargement of epithelial buds. These findings suggest that the magnitude of mechanical stiffness across the lung bud alters the branching pattern. Additionally, physically designed hydrogel material is a valuable tool for producing the specific microenvironment to explore how physical cues affect and alter tissue morphogenesis for in vitro study.

Direct cell-cell interactions control apoptosis and oligodendrocyte marker expression of neuroepithelial cells

2001 ◽  
Vol 65 (3) ◽  
pp. 195-207 ◽  
Author(s):  
J.P. Hugnot ◽  
K. Mellodew ◽  
H. Pilcher ◽  
D. Uwanogho ◽  
J. Price ◽  
...  
Keyword(s):  
Cell Interactions ◽  
Neuroepithelial Cells ◽  
Direct Cell ◽  
Marker Expression ◽  
Cell Cell

Msh homeobox genes regulate cadherin-mediated cell adhesion and cell–cell sorting

1998 ◽  
Vol 70 (1) ◽  
pp. 22-28 ◽  
Author(s):  
John M. Lincecum ◽  
Allison Fannon ◽  
Kening Song ◽  
Yaoqi Wang ◽  
David A. Sassoon
Keyword(s):  
Cell Adhesion ◽  
Cell Sorting ◽  
Homeobox Genes ◽  
Cell Cell

scholarly journals Direct laser manipulation reveals the mechanics of cell contacts in vivo

2015 ◽  
Vol 112 (5) ◽  
pp. 1416-1421 ◽  
Author(s):  
Kapil Bambardekar ◽  
Raphaël Clément ◽  
Olivier Blanc ◽  
Claire Chardès ◽  
Pierre-François Lenne
Keyword(s):  
Cell Shape ◽  
Constitutive Law ◽  
Cell Junctions ◽  
Scale Model ◽  
Tissue Morphogenesis ◽  
Cell Contacts ◽  
Cell Shape Changes ◽  
Shape Changes ◽  
Cell Cell

Cell-generated forces produce a variety of tissue movements and tissue shape changes. The cytoskeletal elements that underlie these dynamics act at cell–cell and cell–ECM contacts to apply local forces on adhesive structures. In epithelia, force imbalance at cell contacts induces cell shape changes, such as apical constriction or polarized junction remodeling, driving tissue morphogenesis. The dynamics of these processes are well-characterized; however, the mechanical basis of cell shape changes is largely unknown because of a lack of mechanical measurements in vivo. We have developed an approach combining optical tweezers with light-sheet microscopy to probe the mechanical properties of epithelial cell junctions in the early Drosophila embryo. We show that optical trapping can efficiently deform cell–cell interfaces and measure tension at cell junctions, which is on the order of 100 pN. We show that tension at cell junctions equilibrates over a few seconds, a short timescale compared with the contractile events that drive morphogenetic movements. We also show that tension increases along cell interfaces during early tissue morphogenesis and becomes anisotropic as cells intercalate during germ-band extension. By performing pull-and-release experiments, we identify time-dependent properties of junctional mechanics consistent with a simple viscoelastic model. Integrating this constitutive law into a tissue-scale model, we predict quantitatively how local deformations propagate throughout the tissue.

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