Stability and switching in cellular differentiation

The international workshop on the Regulability of the Differentiated State was planned as a satellite meeting associated with the IXth International Congress of the International Society of Developmental Biologists held in Basel, Switzerland from August 28th to September 1st 1981. The workshop held in Edinburgh from September 1st to 5th 1981 was able to benefit from the presence in Europe of a number of developmental biologists from Japan and the United States. The workshop was intended to be an opportunity for a limited number of workers from a variety of areas in developmental biology to spend a short time exchanging data and a more prolonged time developing the ideas that arose from the data. Free-ranging discussion was intended right from the initial stages of planning the meeting and the preparation of the proceedings of the workshop gives an opportunity to others to see the directions taken by those discussions. Accordingly we have published here a collection of the formally presented papers; summaries of the discussions which arose from those papers, together with some linking material which the editors believe will be of help to the reader in seeing the significance of some of the ideas which were put forward during the workshop. This linking material has been prepared in Edinburgh. After the contributions were to hand, we came to believe that some of the potential readership might wish to have available introductions to the main-sections, outlining areas not touched on in any of the particular papers and giving a few general references not quoted in these papers. We must apologize to our colleagues and admit with regret to the readers of this book that some interesting points made during discussion have been lost. The recording quality of the tapes, in spite of preliminary testing, turned out to be defective in places. Summary outlines were prepared during the discussions by some speakers, yet participants often, in the heat of discussion, did not find the time to write these out. Apart from the unavoidable gaps we hope that this has not led us accidentally to misrepresent any of the participants. The topic of the regulability of cells which have already undergone a degree of differentiation or, to put it another way, the stability of their differentiated state, has some interest to clinicians, especially to oncologists and pathologists, and it also relates to one of the most lively areas of current biology, namely the way in which the expression of genes is controlled both in normal and abnormal development. The rapid expansion of our knowledge of gene structure and the details of gene transcription and the translation of RNA to give rise to cellular proteins gives an excitement to this area of research, but the organizers believed in the importance of relating this molecular data to current concepts in cell biology and to ideas which have been with us from the earliest days of experimental embryology such as notions of competence and determination. The proceedings published here follow the structure of the conference, with an introductory session aimed at defining and classifying the problems to be discussed, followed by sections on the molecular basis of differentiation and competence; on reversible malignancy, transdifferentiation and related topics; and on strategies of regulation. The final session of the conference was a round-table discussion which pursued in detail a number of important issues which had arisen earlier, in particular the extent to which differentiated cells can modify their gene expression or, after cell division, give rise to progeny expressing genes characteristic of other cell types. The types of molecular mechanism which would explain the balance between stability and plasticity of gene expression were also discussed.