Differentiation 13. 69 ( 1 979) Differentiation 0 Springer-Verlag 1979

And Now What? A Panel Discussion

The symposium ended with a panel discussion led by F. Crick in which perspectives for the near future were considered.

The most puzzling discovery of this last year is that in many eukaryotic genes the coding sequences are in- terrupted by long stretches of nucleotides, the introns. Since these ‘non-coding’ sequences exist, it would be surprising if they had no function, and if they were not implicated in some kind of regulation or fine tuning. The exact function of the introns is at present anybody’s guess, and the panel discussion illustrated some of the ideas or lines of thought stimulated by the few available experimental data.

Split genes are transcribed as a unit giving a long RNA molecule which is spliced to give functional mes- senger RNA with uninterrupted coding sequence. The existence of introns in the genes might conceivably be justified by processes relevant to the genetic material itself, e.g. DNA folding, chromatin structure, chromoso- mal mechanisms, control of differentiation. If so, splic- ing of the transcripts could be regarded as the mere elimination of meaningless RNA sequences, much as formylmethionine having no function in the completed protein is removed from the growing polypeptide.

Conversely, introns might have their ‘raison d’ktre’ in the processing of transcripts giving rise to functional messenger RNA’s. Splicing of the transcripts is known to occur but it has not k n analyzed yet. Control at this level is conceivable; some regulatory proteins might bind to the intervening sequences of the primary tran- scripts, or splicing enzymes might respond to regulatory signals.

The fact that introns are also found in the leader non-coding sequence of some messengers does not help much to defining their function, for the role of the leader sequence of messengers is sti l l poorly understood.

How can the riddle of the introns be solved? A gen- eral impression is that we need mutants with alterations

within the introns, but it is not clear how such mutants can be searched for. Another possible approach would be to concentrate on proteins which associate with pri- mary transcripts.

Synapsis dependent complementation in Drosophila indicates that contacts between chromosomes might have a regulatory function. Introns might conceivably play a part in synapsis. Study of diploid versus haploid cell lines in adequate material like yeast might be a re- warding approach.

Another field was briefly considered: the analysis of cell interactions. Technological advances indeed make it possible to tackle this long lasting problem with comple- tely new possibilities. High resolution gel electrophoresis allows the exhaustive characterization of changes in protein pattern during differentiation in cell culture and organogenesis in embryos. Combination of cloning and cell fusion, introduction of a nucleus or of a single chro- mosome into a cytoplasm offer possibilities which will soon be exploited; they are bound to give fundamental new data on differentiation.

One cannot expect a panel discussion to solve prob- lems, even when its participants are leaders of the field. Too little time was leR for the discussion to be comple- tely relaxed and for the participants to elaborate their ideas in much detail; essentially, the panel discussion brought together ideas which had already been ex- pressed during the regular sessions of the symposium. It had, however, an impact especially on the younger scientists who attended the meeting; it showed them that even the very best and most brilliant and imaginative minds simply do not know much beyond experimental facts; knowledge is acquired by a continuous search in a fog, helped by well established notions, by imagination which should be fearless but not wild, and rewarded now and then by an illuminating discovery.

H. Chantrenne

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