The extracellular matrix guides the orientation of the cell division axis

Abstract

The cell division axis determines the future positions of daughter cells and is therefore critical for cell fate. The positioning of the division axis has been mostly studied in systems such as embryos or yeasts, in which cell shape is well defined. In these cases, cell shape anisotropy and cell polarity affect spindle orientation. It remains unclear whether cell geometry or cortical cues are determinants for spindle orientation in mammalian cultured cells. The cell environment is composed of an extracellular matrix (ECM), which is connected to the intracellular actin cytoskeleton via transmembrane proteins. We used micro-contact printing to control the spatial distribution of the ECM on the substrate and demonstrated that it has a role in determining the orientation of the division axis of HeLa cells. On the basis of our analysis of the average distributions of actin-binding proteins in interphase and mitosis, we propose that the ECM controls the location of actin dynamics at the membrane, and thus the segregation of cortical components in interphase. This segregation is further maintained on the cortex of mitotic cells and used for spindle orientation.

Distinct horizontal patterns in the spatial organization of superficial zone chondrocytes of human joints

“…It has been suggested that chondrocyte groups may have formed during skeletal development (Morrison et al, 2000), and their pairing may have arisen after cell division followed by an incomplete separation within the chondron microenvironment (Chi et al, 2004). The position of daughter cells can be determined by positioning of the cell division axis and is influenced by the spatial distribution of the ECM (Thery et al, 2005). In fact, an electron microscopy study of the articular surface reported associations between ECM surface depressions and superficial cell groups in rabbit cartilage (Clark and Rudd, 1991).…”

The metastatic cancer cell cortex: An adaptation to enhance robust cell division in novel environments?

“…As adherent cells round up upon entry into mitosis, they maintain attachment to this underlying substrate through actin-rich retraction fibers [6]. This integrin-mediated attachment to the ECM has been shown to guide spindle positioning [7,8]. Furthermore, disruption of integrin signaling in mitosis results in defects in centrosome separation and bipolar spindle assembly [9], as well as impaired cytokinesis [9,10].…”

“…Moreover, circulating tumor cells have been reported to express proliferation markers [13]. Then, in order to form metastases, cells must undergo a process of extravasation to leave the blood/lymphatic system to colonize a new tissue environment, where they must proliferate despite differences in matrix composition and mechanics compared with their tissue of origin.microenvironment affect spindle positioning and division [7][8][9][10][11] it is likely that mitosis in a foreign environment presents a challenge. This may explain, in part, why metastasized cells often initially enter a dormant non-proliferative phase when introduced to a new environment [12].…”

Coordinating cell polarity with cell division in space and time

“…By contrast, symmetrically dividing animal cells establish cell matrix adhesions or contacts with neighboring cells and, in vivo, coordinate their division plane with tissue architecture. In vitro, adhesion to the extracellular matrix (ECM) plays a major role in orienting the division plane [22]. HeLa cells grown on coverslips with patterned shapes of fibronectin (e.g.…”