How Does A Millimeter-Sized Cell Find Its Center?
When mitosis occurs, the nucleus is at the center of the cell, and the two daughter cells split symmetrically. But how does the nuclues find the center of the cell? While there seems to be reasonable explanations for small and intermediate sized cells, the mechanism for large (millimeter) sized cells is unclear. This paper proposes a few possibilities.
Below are immunostaining pictures of the egg of a clawed frog Xenopus laevis during its first cell cycle after fertilization. At time t=0 the sperm enters the egg, and at time t=1 the first cleavage occurs.
The sperm upon entering the cell carries with it a centrosome from which a radial network of microtubules grow. This network, called the sperm aster, somehow moves the centrosome towards the center of the cell. When a microtubule touches the female nucleus, it is somehow pulled to the center of the aster. Thus by the end of the sperm aster growth the genetic material of both the sperm and the egg are at the center of the cell. The sperm aster breaks down and the mitotic spindles are formed. Then two astral microtubules begin to grow and move towards the centers of the new cells, bringing the genetic material of the daughter cells with them. This paper studies how the asters are able to locate the center of the cell.
Finding the Center: Proposed Models
The paper discusses four possible methods by which the asters can find the center of the cell.
A. Simple Microtubule Pushing According to this model the microtubules grow out radially from the aster center until they reach the cell boundary. At the boundary, they keep growing, thereby pushing the aster center away. Therefore the side of the cell where the aster starts out will have many microtubules touching that edge, and they will push the center away. A microtubule is only able to sustain a certain amount of force due to buckling, and this force is proportional to <math>1/L^2</math> where L is the length of the microtubule. Another way to explain how the aster centers might be that the center might have microtubules attached to different parts of the cell boundaries, but the microtubules that are longer aren't able to push as hard as the shorter microtubules, so the center moves away from the cell boundary it is closest to and zeroes in on the center.
While this model is believed to be the mechanism by which aster centering occurs in small cells such as fission yeast cells, the model doesn't work as great for larger cells like the frog egg. The length the microtubules must grow for these cells is larger, and so the pushing force is very weak. The cell would need a very large amount of microtubules to use this mechanism to push the aster to the center, and this is not observed.
B. Pushing with a stiffened microtubule meshwork This model works much the same as the previous, except here microtubules do not act alone but as bundles. If microtubules are tightly bundled together, they can increase their stiffness and therefore sustain a much higher force. Instead of curving under buckling, they would form bends, thereby creating a meshed network. There have been observations that the density of microtubules is higher at the radial edges of the aster center as compared with at its center. This would not make sense if all the microtubules are connected to the aster center. However, if the microtubules were able to somehow replicated and form parallel rods near their growing ends, they could form microtubule bundles. While the mechanism by which this could happen is not known, it makes this model a possible explanation for the aster centering.
C. Pulling from the cortex with limited attachment sites This is the currently accepted mechanism for aster centering in intermediate sized cells, such as C. elegans and budding yeast. In this model, the microtubles grow out radial from the aster center until they hit the cell boundary. Once there, cortical motors pull on the microtubules, thus pulling the aster towards the edges of the cell. If the aster starts out near one side of the cell, more microtubules will hit that side, and so one would naively think that there would be more microtubules pulling it that side, failing at centering the aster. However, if there are a limited number of anchoring sites for the microtubules, then more anchoring sites will be found on the boundary of the cell far away from the decentered aster, thereby pulling the aster towards the center.
However, the paper points out that this model seems to be inconsistent with the data seen from the frog cell. The aster starts moving towards the center well before the microtubules hit the far edge of the cell, so there is no way for the microtubules to be pulling it to the center.
D. Pulling on the cytoplasm The final model discussed by the authors proposes that there are molecular motors distributed throughout the cytoplasm. These molecular motors must be attached to something stationary (for example, yolk or other cytoskeletal polymers) and must be able to pull the microtubules by moving towards the 'minus' end of the microtubule. Presumably, a longer microtubule would have more motors attached to it, and therefore would be able to generate a larger pulling force. In this way the if the aster is centered on one side of the cell, the microtubules will be longer in the direction of the far side of the cell, and so will be able to pull the aster towards the center.
The problem with this model is that the cytoplasm must be stiff enough for the motors to be stationary, but yet fluid enough for the aster to move through it. The authors suggest a possible solution: perhaps the centrosomes can 'melt' the cytoplasm in their immediate vicinity, thus able to move through the otherwise stiff cytoplasm.