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First published online December 31, 2008
doi: 10.1242/10.1242/jcs.018945

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Integrins and cell-fate determination

Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK

View larger version (11K): [in this window] [in a new window]   Fig. 1. Multiple points in the control of cell cycle and fate by integrins. The points in the cell cycle at which integrins have an essential role are shown in pink, and include G1, metaphase and telophase. The fates of daughter cells are also integrin-dependent. They become committed to (a) re-enter the cell cycle, (b) survive or apoptose or (c) express tissue-specific genes and differentiate. (d) In the case of stem cells, one daughter cell will enter the cell cycle and then undergo one of the three fates shown in (a-c), whereas the other will remain a stem cell.

View larger version (50K): [in this window] [in a new window]   Fig. 2. Integrins orient the cell-division axis. (A) The mitotic spindle aligns along the long axis of the cell, which lies at right angles to the plane of cytokinesis. A mitotic cell is shown, and the microtubule connections between the cell edge (cortex, plasma membrane) and spindle poles, and between the spindle poles and chromosomes (which accumulate at the metaphase plate) are highlighted. (B) Cells adhere to the ECM through integrins. They can either divide along the plane of the ECM (turquoise in panels C-E) to which they adhere (x- or y-axes), or away from it (z-axis). (C,D) Tension provided along the x-axis causes unilateral extension (C), which becomes bilateral if tension is also provided in the y-axis (D), forming a sheet of cells. (E) Orientation of the plane of division along the z-axis causes cells to become displaced away from the initial ECM. These new (purple) cells have a microenvironment that is different to the parental (pink) cells. Thus, following cell division, daughter cells become located either in a similar niche to their parents, or in a new microenvironment.

View larger version (27K): [in this window] [in a new window]   Fig. 3. Retraction fibres provide resistive forces to orient the mitotic spindle. (A) Interphase cell, showing sites of attachment to the ECM via integrin adhesions and the intracellular cytoskeleton. This is the view that is seen when looking down on cells in 2D culture. (B) Mitotic cell that has rounded up in preparation for cytokinesis. The cell remains attached to the substratum through retraction fibres, which provide resistance so that tension can build up within microtubules and thereby orient the spindle.

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