Different strokes

Different strokes THE development of a multicellular organism begins with a fertilised egg and proceeds through a series of inter- mediate steps -growth, cell division, differentiation into specialised parts, and so on -before culminating in the adult. An important part of the process is what is called pattern formation, the orderly arrangement of tissues leading to {often) a visually pleasing appear- ance. The spots on a cheetah, the stripes on a zebra and the markings on a butterfly's wings are all examples of developmental pattern.

Since a long time, a popular hypothesis to explain the origin of patterns has invoked the existence of what are called morphogens, chemical substances or signals responsib1e for patterns. The past few years, in the course of which a number of candidate morphogens have been identified, have seen a vindication of the morphogen hypothesis.

One such morphogen goes by the name of DIF, for differentiation-inducing substance. It is a chlorinated phenolic derivative and was initially thought of as being responsible for the differentiation of a specific cell type in the primitive multicellular amoeba or the cellular slime mould Dictyuostelium discoideum. The slime mould gives rise to just two cell types: a dead cell or stalk, and a hibernating cell or spore.

It appeared that DIP could specifically induce stalk cell differentiation and repress the differentiation of spores. This finding led to the suggestion that the distribution of DIP in the multicellular mass was probably responsible for the belief that wherever its levels were high, amoebae turned into stalk, and wherever they were low, they formed spores. A number of subsequent results, however, have demonstrated that the real picture is far more intricate.

To begin with, it was discovered that the spatial distribution of DIP was exactly opposite to that predicted; amoebae that contained high levels of DIP formed spores and the ones that contained low levels formed stalk. This finding was augmented by another discovery which said that the stalk-forming amoebae took active steps to get rid of DIP by synthesising an enzyme that could break it down; the argument was that they were so sensitive to DIP that they were trying to defend themselves -evidently with- out success -from its lethal action.

Recent work by Akiko Oohata of the Kansai Medical University in Osaka, Japan, shows that DIP is not a stalk-specific inducer after all. Her experiments make use of the known fact that if amoebae are spread out at very low densities -below about 1,000 per sq cm - they do not differentiate at all, presumably because they are too far off from one another to be able to communicate and decide on an agreed plan for differentiation.

However, if certain chemicals are added or applied externally, the amoebae do differentiate into presumptive spore cells. Oohata found that conditioned medium, meaning a solution of salts in which cells were kept shaken for a long while, was an excellent inducer of differentiation at these low cell densities. When she went on to purify the active principles in conditioned medium, she discovered that one was a new factor of fairly largish molecular weight (about 180,000 Daltons); the other, surprisingly, was DIF.

It appears that at lower concentrations DIP leads to the movement of cells into the spore pathway. Only at higher concentrations does it start to induce stalk differentiation. Also, once cells have set off in a pre-spore defection, they become resistant to DIP. These remain plausible speculations for the moment. What is interesting is that a system as simple as this is exhibiting such a level of sophistication in terms of the logic underlying its development.

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