Animals --- chicken, humans, mice, flies, worms --- all develop from a fertilised egg.  The egg divides to give two daughter cells. The daughter cells each divide. And then divide again.

  How do daughter cells decide what to become? Who makes hair? Muscle? Brain? Each cell in the brain is different from its neighbour. What are the mechanisms that decide the fate of cells?
 

How Do Cells Decide Their Fate?

    There are two simple models one can construct. In the lineage model, a cell's fate is decided by its parentage --- this is also called the British model. Success in Britain is supposedly decided by who your parents are. The second model is the neighbourhood model --- this has also been called the American model. Success in America is supposedly determined by the neighbourhood in which you stay; and your parentage is irrelevant.
 

The Developing Egg Can be Watched

    In some animals, such as the roundworm, development can be watched as it happens. Each cell can be seen dividing. Its daughters can be seen doing the same and, with very careful observation, the entire lineage of the roundworm can be traced. 

    We know the origins of each and every cell in the mature worm. We know who its parent cells were. And who their parents were.

    Sometimes some daughter cells are programmed to die (the ones marked with a cross). Others divide faster than their neighbours. But what is remarkable about the roundworm is that all these processes appear invariant. By "invariant" we mean that the lineage which gives rise to the mature worm is the same from worm to worm. It would appear that the roundworm is an example of the lineage model.

    However, just because parentage of each mature cell is invariant, does that mean that parentage is what determines cell fate?
 

Testing Lineage Versus Neighbourhood Theories

    If parentage were all that mattered, killing a parent cell will result in its progeny being absent and cells of that "fate," i.e. cells of fates c and d (in the picture below), should be missing in the mature animal.

    However, it could be that lineage is incidental. That fates c and d might be determined by cell e talking to its neighbours.

    Cell e could make a chemical which tells its nearest non-sibling neighbour to become d; the one further away in the same direction, c; and so on.  In that case, removing e will have a dramatic effect on the fates of cells that would normally become c and d. But removing c and d's parents may result in other neighbouring cells, such as a and b, to take on the fates of c and d.

    We will next deal with the possible molecular mechanisms by which lineage and neighbourhood influences can act.
 

Inheritance

    We can give one sibling cell a label, say P. When cells divide they can inherit their labels, and do not have to find them afresh.  The daughters of P cells are P. And the daughters of cells without the P label are not P, and are therefore, say, A. 

    When the cells complete some rounds of division they can take on labels other than just P.  Cells with a P label can confer labels i, j, k, l, m, n, o and p.  Cells with an A label can, similarly, confer labels a, b, c, d, e, f, g, and h. We will discuss later how this might happen. What we have done so far now is to restrict the range of choice that cells have, by giving sibling cells and their daughters two different inheritable labels.

    Giving a cell a P label can be done by turning ON a switch that results in P being made in the cell. But once the switch is turned on, P can also do the job of keeping the switch in the ON state. Thus P can be the label, as well as being the factor that is required for keeping the switch in the ON state. This ensures that P is made in daughter cells and the original factor that was used to make P need no longer be present.

    There are several simple ways in which the P label can be first made. One way, is by asymmetric inheritance. The factor that is required to turn ON the regulatory switch may be localised in one part of a mother cell (perhaps at too low a local concentration to function here and turn on P). Upon cell division, this asymmetric localisation may result in asymmetric inheritance. Thus, the P label is made in one daughter and not in the other because the switch to make P can be turned to the ON state in only one daughter.

    We will next examine how neighbourhood influences can confer labels. That will help us understand how the P labelled cells can confer a defined range of labels such as i, j, k, l, m, n, o and p.
 

Influence

    Cells can influence their neighbours. They can influence cells they touch. Cells nearby, and cells far away. In each case, although the specific mechanisms vary, the principle is the same.

    A signal reaches the outside of a cell. This information is transmitted to the inside of the cell. In response to this information, the cell switches on a label. The intensity and direction of the signal could both be sensed by the cell.
 

Signalling by contact 

    One situation in which signalling by contact is used, is to generate differences amongst a sheet of equivalent cells.

    Short-range signals typically act over few (<10) cell diameters. The source of the signal could be cells of a particular label (P) and the signal could be such that it cannot be sensed by cells that generate it. The signal will be strong near the source and will act to switch on a specific label at high concentration.

    Further away from the source, the signal will be weaker and will switch on another label in cells which sense this weaker signal.

Long-range signals

   These signals can act over tens of cell diameters. One way in which long-range signals are generated is in response to a short-range signal. 

    Cells which see a short-range signal could generate a long-range signal. The long-range signal can also specify labels according to the concentration of signal  sensed by a cell.

Long-range signals can affect the source of the short-range signal

    In our example, the short range signal came from P-cells. The signal acted on non-P cells (that is, on A cells), near the source of this signal, to generate a long- range signal. The long-range signal acted on A cells to generate labels.  The long-range signal could, in addition, pattern P cells.  Thus, depending on whether cells have a P label or an A label, the long-range signal has different consequences.

 

The pictures flanking the title are of the caterpillar of the Monarch butterfly.
To see a large image of one these click here.

End of the Making Animals page