Interplay of Cell Shape and Division Orientation Promotes Robust Morphogenesis of Developing Epithelia

Xiong, Fengzhu; Ma, Wenzhe; Hiscock, Tom W.; Mosaliganti, Kishore; Tentner, Andrea R.; Brakke, Kenneth A.; Rannou, Nicolas; Gelas, Arnaud; Souhait, Lydie; Swinburne, Ian A.; Obholzer, Nikolaus; Megason, Sean G.

doi:10.1016/j.cell.2014.09.007

Cited by 114 publications

(111 citation statements)

References 70 publications

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“…Based on these results, we suggest cells chart different differentiation and behavioral pathways by sensing/altering their cytoplasmic volume and density through changes in water influx/efflux. the cytoplasm and cell surface and use confocal microscopy to identify the boundaries of the cell in 3D (12,13). The measured volumes have been shown to be consistent with those measured by atomic force microscopy (AFM) (8).…”

Section: Significancementioning

confidence: 62%

Cell volume change through water efflux impacts cell stiffness and stem cell fate

Guo

Pegoraro

Mao

et al. 2017

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

395

450

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Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its volume decreases, while its stiffness concomitantly increases. We find that both cortical and cytoplasmic cell stiffness scale with volume for numerous perturbations, including varying substrate stiffness, cell spread area, and external osmotic pressure. The reduction of cell volume is a result of water efflux, which leads to a corresponding increase in intracellular molecular crowding. Furthermore, we find that changes in cell volume, and hence stiffness, alter stem-cell differentiation, regardless of the method by which these are induced. These observations reveal a surprising, previously unidentified relationship between cell stiffness and cell volume that strongly influences cell biology.cell volume | cell mechanics | molecular crowding | gene expression | stem cell fate C ell volume is a highly regulated property that affects myriad functions (1, 2). It changes over the course of the cell life cycle, increasing as the cell plasma membrane grows and the amount of protein, DNA, and other intracellular material increases (3). However, it can also change on a much more rapid time scale, as, for example, on cell migration through confined spaces (4, 5); in this case, the volume change is a result of water transport out of the cell. This causes increased concentration of intracellular material and molecular crowding, having numerous important consequences (6, 7). Alternately, the volume of a cell can be directly changed through application of an external osmotic pressure. This forces water out of the cell, which also decreases cell volume, increases the concentration of intracellular material, and intensifies molecular crowding. Application of an external osmotic pressure to reduce cell volume also has other pronounced manifestations: For example, it leads to a significant change in cell mechanics, resulting in an increase in stiffness (8); it also impacts folding and transport of proteins (9), as well as condensation of chromatin (10). These dramatic effects of osmotic-induced volume change on cell behavior raise the question of whether cells ever change their volume through water efflux under isotonic conditions, perhaps to modulate their mechanics and behavior through changes in molecular crowding.Here, we demonstrate that when cells are cultured under the same isotonic conditions, but under stiffer extracellular environments, they reduce their cell volume through water efflux out of the cell, and this has a large and significant impact on cell mechanics and cell physiology. Specifically, as a cell spreads out on a stiff substrate, its volume decreases, and the cell behaves in a similar manner to that observed for cells under external osmotic pressure: Both the cortical and cytoplasmic stiffness increase as the vol...

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Section: Significancementioning

confidence: 62%

Cell volume change through water efflux impacts cell stiffness and stem cell fate

Guo

Pegoraro

Mao

et al. 2017

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

395

450

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“…The reduction in cell number could be caused by decreased EVL cell proliferation or EVL cell loss, with a concomitant expansion of EVL cell size to compensate for the deficiency. Such compensation through EVL cell size alterations has been described previously (Sonal et al, 2014;Xiong et al, 2014). The cause of the reduced EVL cell number might reflect other deficiencies of the EVL, which could also contribute to the morphogenesis defects observed in these mutants.…”

Section: Evl Defectsmentioning

confidence: 92%

Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis

et al. 2016

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The vertebrate embryonic dorsoventral axis is established and patterned by Wnt and bone morphogenetic protein (BMP) signaling pathways, respectively. Whereas Wnt signaling establishes the dorsal side of the embryo and induces the dorsal organizer, a BMP signaling gradient patterns tissues along the dorsoventral axis. Early Wnt signaling is provided maternally, whereas BMP ligand expression in the zebrafish is zygotic, but regulated by maternal factors. Concomitant with BMP activity patterning dorsoventral axial tissues, the embryo also undergoes dramatic morphogenetic processes, including the cell movements of gastrulation, epiboly and dorsal convergence. Although the zygotic regulation of these cell migration processes is increasingly understood, far less is known of the maternal regulators of these processes. Similarly, the maternal regulation of dorsoventral patterning, and in particular the maternal control of ventral tissue specification, is poorly understood. We identified split top, a recessive maternal-effect zebrafish mutant that disrupts embryonic patterning upstream of endogenous BMP signaling. Embryos from split top mutant females exhibit a dorsalized embryonic axis, which can be rescued by BMP misexpression or by derepressing endogenous BMP signaling. In addition to dorsoventral patterning defects, split top mutants display morphogenesis defects that are both BMP dependent and independent. These morphogenesis defects include incomplete dorsal convergence, delayed epiboly progression and an early lysis phenotype during gastrula stages. The latter two morphogenesis defects are associated with disruption of the actin and microtubule cytoskeleton within the yolk cell and defects in the outer enveloping cell layer, which are both known mediators of epiboly movements. Through chromosomal mapping and RNA sequencing analysis, we identified the lysosomal endopeptidase cathepsin Ba (ctsba) as the gene deficient in split top embryos. Our results identify a novel role for Ctsba in morphogenesis and expand our understanding of the maternal regulation of dorsoventral patterning.

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“…Note characteristic differences in cell shape. (Xiong et al, 2014). In the airway epithelium, similarly, overcrowding due to proliferation and migration induces Piezo1-dependent extrusion of live cells out of the cell plane (Eisenhoffer et al, 2012).…”

Section: Cell Shape and Cell Proliferationmentioning

confidence: 99%

Collective migration and cell jamming in asthma, cancer and development

Park

Atia

Mitchel

et al. 2016

Journal of Cell Science

138

169

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Collective cellular migration within the epithelial layer impacts upon development, wound healing and cancer invasion, but remains poorly understood. Prevailing conceptual frameworks tend to focus on the isolated role of each particular underlying factor -taken one at a time or at most a few at a time -and thus might not be tailored to describe a cellular collective that embodies a wide palette of physical and molecular interactions that are both strong and complex. To bridge this gap, we shift the spotlight to the emerging concept of cell jamming, which points to only a small set of parameters that govern when a cellular collective might jam and rigidify like a solid, or instead unjam and flow like a fluid. As gateways to cellular migration, the unjamming transition (UJT) and the epithelial-to-mesenchymal transition (EMT) share certain superficial similarities, but their congruence -or lack thereof -remains unclear. In this Commentary, we discuss aspects of cell jamming, its established role in human epithelial cell layers derived from the airways of nonasthmatic and asthmatic donors, and its speculative but emerging roles in development and cancer cell invasion.

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Interplay of Cell Shape and Division Orientation Promotes Robust Morphogenesis of Developing Epithelia

Cited by 114 publications

References 70 publications

Cell volume change through water efflux impacts cell stiffness and stem cell fate

Cell volume change through water efflux impacts cell stiffness and stem cell fate

Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis

Collective migration and cell jamming in asthma, cancer and development

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