Biology Reference
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to the process under discussion. They might modulate extent or robustness but are assumed
not to be critical to whether the morphogenetic event can take place at all. It is very difficult to
test at the bench whether the basic pathway drawn really is sufficient. Simply knocking out
the other possible interacting molecules, apart from being an unrealistically massive under-
taking, would not help because these molecules, even if they have no direct connection to
morphogenesis, may nevertheless be critical to keeping the cell alive. Similarly, forcing the
molecules of the pathway in question to be expressed in other cells of the same organism,
and testing whether these cells now undergo the morphogenetic event, suffers the problem
that many of the other interacting molecules will also be present in the new cells. Hypotheses
based on things other than molecular pathways, for example on physical forces, suffer the
same problems: cells generate and respond to forces in many ways and it is difficult to study
the ones thought to be relevant to morphogenesis in isolation.
One way to test the feasibility of a hypothetical morphogenetic system is to model it in
some other system, typically (though not always) a computer-based simulation. Within
such a simulation, 'cells' are reduced to very abstract and simple entities with most of their
normal functions ignored. These basic model 'cells' will be equipped with a representation of
the states of molecules in the pathway, of diffusion of signalling molecules where relevant,
and of the generation of mechanical forces where relevant. The system will be provided
with any necessary field or boundary conditions (for example, a morphogen gradient) and
then left to respond. If the collection of 'cells' does what it is meant to (for example, move
up-gradient, to condense, or make branching trees) then the hypothesis seems at least
feasible. If the collection of cells fails to do what it is meant to then something is wrong, either
with the hypothesis or the simulation.
An example of this type of hypothesis testing is provided by models of cell aggregation by
Dictyostelium discoideum amoebae. As has been described in Chapter 9, D. discoideum has a life
cycle that alternates between unicellularity and multicellularity. When food is plentiful, cells
exist as individual amoebae (
Figure 25.3
a). When food is absent, the amoebae become chemo-
tactic for cAMP and, when they detect it, they also secrete it. A few cells, called 'pacemakers',
become autonomous producers of cAMP pulses and each acts as a centre for all of the other
(non-pacemaker) cells (
Figure 25.3
.b). The amoebae move towards the pacemakers chemo-
tactically and relay the signals, recruiting yet more cells. This results in the formation of
a multicellular aggregate of up to 100,000 cells that is the basis for the multicellular phase
FIGURE 25.3
Aggregation by Dictyostelium discoideum. (a) Cells exist as separate amoebae in the presence of
plentiful bacterial food (fine dots). (b) Under starvation conditions, a pacemaker cell secretes pulses of cAMP and
other cells are chemotactic for this and relay it. (c) The result is streaming, sometimes spiralling, aggregation.
