Differential adhesion in morphogenesis: a modern view

Steinberg, Malcolm S.

doi:10.1016/j.gde.2007.05.002

Cited by 348 publications

(294 citation statements)

References 39 publications

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“…5) mimics the classical sorting behavior of cells that express variable levels of cadherins (31,32). The E-cadherin (Cdh1) repressor Snail (33) was expressed at higher levels in ExEn cells compared with their ES cell progenitors with concomitant Cdh1 down-regulation (Fig.…”

Section: Significancementioning

confidence: 84%

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Arf tumor suppressor and miR-205 regulate cell adhesion and formation of extraembryonic endoderm from pluripotent stem cells

Finkelstein

Sherr

2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance The Arf tumor suppressor gene is not expressed in most normal tissues but when activated by oncogenic stress signals engages a p53-dependent transcriptional program that prevents tumor formation. Surprisingly, expression of the p19 Arf protein in mouse embryoid bodies is required for the timely formation of extraembryonic endoderm (ExEn). Inactivation of Arf down-regulates a single microRNA, miR-205, which can “rescue” ExEn formation in Arf -null embryonic or induced pluripotent stem cells. During ExEn formation, miR-205 regulates a suite of genes that govern cell migration and adhesion, suggesting a conceptual basis for linking the roles of Arf in ExEn differentiation and tumor metastasis.

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Section: Significancementioning

confidence: 84%

“…Adhesion in tissues is predominantly mediated by cadherins, whose quantitative differences in expression are sufficient to govern the spontaneous self-sorting behavior of two cell populations, rendering them immiscible (32). E-cadherin is required for aggregation of ES cells and for the proper formation of EBs (36).…”

Section: Discussionmentioning

confidence: 99%

Arf tumor suppressor and miR-205 regulate cell adhesion and formation of extraembryonic endoderm from pluripotent stem cells

Finkelstein

Sherr

2013

Proc. Natl. Acad. Sci. U.S.A.

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“…In development, differential adhesion has been shown to play an important role in cell sorting (61)(62)(63), and the reorganization of intercellular forces in this context is entirely unexplored. Furthermore, in wound healing, we expect strong cell-ECM forces to be generated at a wound edge due to the local loss of intercellular adhesion.…”

Section: Discussionmentioning

confidence: 99%

Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces

Mertz¹,

Che²,

Banerjee³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

218

201

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Cell-cell and cell-matrix adhesions play essential roles in the function of tissues. There is growing evidence for the importance of cross talk between these two adhesion types, yet little is known about the impact of these interactions on the mechanical coupling of cells to the extracellular matrix (ECM). Here, we combine experiment and theory to reveal how intercellular adhesions modulate forces transmitted to the ECM. In the absence of cadherin-based adhesions, primary mouse keratinocytes within a colony appear to act independently, with significant traction forces extending throughout the colony. In contrast, with strong cadherin-based adhesions, keratinocytes in a cohesive colony localize traction forces to the colony periphery. Through genetic or antibody-mediated loss of cadherin expression or function, we show that cadherin-based adhesions are essential for this mechanical cooperativity. A minimal physical model in which cell-cell adhesions modulate the physical cohesion between contractile cells is sufficient to recreate the spatial rearrangement of traction forces observed experimentally with varying strength of cadherin-based adhesions. This work defines the importance of cadherin-based cell-cell adhesions in coordinating mechanical activity of epithelial cells and has implications for the mechanical regulation of epithelial tissues during development, homeostasis, and disease. mechanotransduction | traction force microscopy M echanical interactions of individual cells have a crucial role in the spatial organization of tissues (1, 2) and in embryonic development (3-5). The mechanical cooperation of cells is evident in dynamic processes such as flow-induced alignment of vascular endothelial cells (6) and muscle contraction (7). However, mechanical interactions of cells within a tissue also affect the tissue's static mechanical properties including elastic modulus (8), surface tension (9), and fracture toughness (10). Little is known about how these tissue-scale mechanical phenomena emerge from interactions at the molecular and cellular levels (11).Tissue-scale mechanical phenomena are particularly important in developmental morphogenesis (12), homeostasis (13), and wound healing (14) in epithelial tissues. Cells exert mechanical force on each other at sites of intercellular adhesion, typically through cadherins (15, 16), as well as on the underlying extracellular matrix (ECM) through integrins (17-19). Cadherin-based adhesions can alter physical aspects of cells such as the surface tension of cellular aggregates (20) and the spreading (21) and migration (22) of single cells adherent to cadherin-patterned substrates. Integrity of intercellular adhesions may also contribute to metastatic potential (23). We and others have shown that epithelial cell clusters with strong cell-cell adhesions exhibit coordinated mechanical behavior over length scales much larger than a single cell (24-27). Several studies have implicated cross talk between cell-ECM and cell-cell adhesions (28, 29) that can be modulated by ac...

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“…This sorting behavior may be relevant to understanding cell intercalation movements during convergent extension and other rearrangements. The differential cell adhesion hypothesis [41] has been the predominant model but the importance of cortical surface tension was recently recognized [42]. Krieg and colleagues [43]* used atomic force microscopy to measure both adhesive strength and cellcortex tension in individual zebrafish gastrula cells from the 3 primary germ layers.…”

Section: Adhesion-dependent Mechanotransduction and Morphogenesismentioning

confidence: 99%

Cell adhesion receptors in mechanotransduction

Schwartz

DeSimone

2008

Current Opinion in Cell Biology

363

298

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Integrins and cadherins are tri-functional: they bind ligands on other cells or in the extracellular matrix, connect to the cytoskeleton inside the cell, and regulate intracellular signaling pathways. These adhesion receptors therefore transmit mechanical stresses and are well positioned to mediate mechanotransduction. Studies of cultured cells have shown that both integrin-and cadherin-mediated adhesion are intrinsically mechanosensitive. Strengthening of adhesions in response to mechanical stimulation may be a central mechanism for mechanotransduction. Studies of developing organisms suggest that these mechanisms contribute to tissue level responses to tension and compression, thereby linking morphogenetic movements to cell fate decisions.

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Differential adhesion in morphogenesis: a modern view

Cited by 348 publications

References 39 publications

Arf tumor suppressor and miR-205 regulate cell adhesion and formation of extraembryonic endoderm from pluripotent stem cells

Arf tumor suppressor and miR-205 regulate cell adhesion and formation of extraembryonic endoderm from pluripotent stem cells

Cadherin-based intercellular adhesions organize epithelial cell–matrix traction forces

Cell adhesion receptors in mechanotransduction

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