Cell division: Decrypting the orientation of cell division axis

At the Institut Curie, two CNRS teams have just reported crucial information on the orientation of cells as they divide. The cell division axis determines not only the position of the daughter cells but also their contents and hence their fate. The researchers have shown that the orientation of division depends on focal adhesions of the cell with its surroundings. They have also identified a new molecule that controls the localization of cellular determinants of so-called asymmetric cell division, thus giving rise to two different cells.

These two studies published in the October and November 2005 issues of Nature Cell Biology shed new light on one of the essential mechanisms in the life of a cell whose deregulation may give rise to cancer.

Division is an essential stage in the life of all cells: it participates in the body’s growth, wound repair, combating infection and in cell turnover. Within our bodies at any given moment some 250,000 million cells are dividing, that is 250,000 million mother cells are in the process of forming 500 000 million daughter cells. As individuals, however, we observe no change. This is because each newly formed cell has a well determined location. The mother cell has a given place among other cells in a tissue and, to avoid perturbing this organization, the daughter cells it produces are also appropriately placed. This very precise positioning is indispensable in maintaining the shape of our tissues and organs. The constraints imposed by the environment influence the division and position of the daughter cells.

Micropatterns control cell adhesion

Manuel Théry in the CNRS team of Michel Bornens(1) has developed an original approach to the study of the effect of space and spatial limitations on the division of adherent cells. By using a micropatterning technique, he imposes the same contour on cells while giving them different adhesion zones. Then, he observes by videomicroscopy how the cells divide. These restrictions reproduce the spatial information that a cell is likely “to sense” within a tissue.

In this way it has been demonstrated for the first time that adhesion proteins play a key part in the orientation of cell division.

Thus, the axis of cell division is oriented as a function of its points of adhesion to its surroundings: the cell can adopt the same shape in different micropatterns, but as this involves different focal adhesions, the orientation of the division is not the same. The focal adhesions govern the distribution of the actin cytoskeleton associated with the cell membrane and impose a specific spindle orientation: when the cell divides, it radically changes shape but keeps at its surface the memory of its focal adhesions. This memory enables orientation of the spindle axis.

This work shows that a protein(2), which is often perturbed in highly metastatic cancer cells, is involved in the orientation of cell division, and this could favor the dissemination of tumors.

This highly original approach therefore yields new findings on cell division and on the mechanisms that ensure it proceeds correctly. It also verifies whether the cells respond correctly to their environment at the time of division, and also helps to understand why the division of tumor cells is perturbed not only temporally but also spatially (orientation within tissue).

Understanding asymmetric division

The two cells formed by the division of a mother cell are not always identical. In the embryo, for instance, division gives rise to various cell types that form the different organs. Likewise, an adult stem cell gives rise to a specialized cell and to a new stem cell, thereby ensuring the conservation of this indispensable cellular type throughout life.

The CNRS team of Yohanns Bellaïche(3) at the Institut Curie are studying these asymmetric divisions in an attempt to understand how the mother cell produces two distinct cells. This sharing of the cell’s contents into two different portions is linked to the orientation of cell division, since the division axis determines how the mother cell splits.

Bellaïche and colleagues have shown that the protein Ric8 plays a key part in the positioning of the division spindle in Drosophila cells. Depending on this axis, the cellular components are separated into two distinct or identical parts.

Complementary views of cell division

Whereas the first study shows which factors determine the orientation of cell division, the second reveals the protein that switches these factors on. These two, fully complementary studies from the Institut Curie afford a new vision of cell division, and in particular of its orientation, a key point in development of the embryo and in correct tissue function in the adult.

These new fundamental data on cell division, whose disruption leads to cancer, are essential for a better understanding of how a cell becomes tumoral.