Research in the field of planarian regeneration on the one hand, and a general survey of embryology on the other, throw doubt upon the reality of supra-cellular controls, which are still at the basis of all modern concepts of morphogenesis. The necessity of referring to such controls, which have never been convincingly demonstrated, is probably due to the fact that two aspects of cell behaviour have been underestimated: 1) the capacity of cells to change their individualities for a time independently (...) of other cells; 2) the social behaviour of cells, which is the consequence of the reciprocal exchange of information. Pattern formation and pattern remodeling in normal development results from readjustments of cell populations to local or global changes. The common responses of cell populations to disturbances are enhanced mitotic activity, cessation of specific syntheses and cell migration. In the young embryo these may promptly restore the unity of the injured primordium, leading to so-called restitution; this is based on a normal sequence of further readjustments in the primordium. In older organisms the same responses give rise to cell interactions which may be the starting point for further sequential readjustments — in some instances these are comparable to those that originally organized the primordium in question during development. The desirability of giving up the notion of morphogenetic field is discussed. (shrink)

The control of pattern formation and the significance of gradients is reconsidered on the basis of the concept of cell sociology (which takes into account continuous exchange of information between cells and the possibility of autonomous progression in differentiation). Not all traits of a pattern are imposed by a single prepattern, which would be an organized molecular framework or a gradient. Patterns are unfolded in steps; these are readjustments of a cell population to intrinsic and extrinsic changes in cell activities. (...) Prepatterns are the various components of the programme of every readjustment and are established by information of various origins, which can be dissociated experimentally: determination (elementary social prepattern), pre-existing organization (antecedent pp.), surrounding cell populations (environmental pp.), position among other tissues (positional pp.) and the organization of inducers (imprinting pp.). Every transitory pattern formed during a readjustment serves as antecedent pp. during the next readjustment. Covert graded patterns result from various aspects of the social behaviour of cells (growth, aggregation, induction, cell renewal) and may serve as antecedent or imprinting prepatterns. They appear as water marks in the final patterns, or generate overt graded patterns. They also manifest themselves in temporal patterns, particularly in gradients of relative growth. (shrink)

The principles of automation (automatism and programming) in the unfolding of spatio-temporal patterns during animal development are deduced from experimental data reconsidered from the point of view of cell sociology. The developmental programme in the egg is not part of the genetic information but a part of the cytoplasmic information. Throughout development cells store extra-cellular information released by their neighbours in the form of cytoplasmic information. Successive determinations cannot be considered as successive reprogrammings of cells: each one consists of a (...) selection of one specific programme from the total information previously stored. This programme specifies cell interactions in the determined population as a whole; it is very imprecise and is progressively completed during the course of further differentiation by information released by neighbouring cell populations. Complicated patterns may emerge from only two homogeneous populations involved in distinct differentiation pathways and confronting each other. Consequently the egg developmental programme provides gene effectors and specific physico-chemical conditions necessary for the starting of at least two distinct differentation pathways. Experimental data suggest that there are two components in this programme. One is a molecular machinery which starts at fertilization in the whole cytoplasm. It yields two programmes of differentiation, typically first an endodermal and then an ectodermal one. The other component of the egg developmental programme, which does not require specific information, allows the interception of the first (endodermal) programme. The application of informatics to developmental automatism is discussed in the latter part of the paper. (shrink)

This article is concerned with the problem of the relation between the genetic information contained in the DNA and the emergence of visible structure in multicellular animals. The answer is sought in a reappraisal of the data of experimental embryology, considering molecular, cellular and organismal aspects. The presence of specific molecules only confers a tissue identity on the cells when their concentration exceeds the threshold of differentiation. When this condition is not fulfilled the activity of the genes that code for (...) the specific molecules in question only confers on them a histogenetic potency, i.e. the capacity to form the corresponding tissue in further development (or to transdifferentiate to that tissue). The progressive restriction of histogenetic potencies during development reflects the irreversible repression of more and more genes. The establishment of a given tissue identity under the influence of an inducing tissue (or a morphogenetic hormone) is only possible when the cells have acquired the competence to respond. Tissue differentiation proceeds progressively during development thanks to the cytoplasmic memory that cells retain collectively (or sometimes individually) of the items of information successively registered by their ancestors cells. The increasing complexity of visible structure emerging during development results only from the progression of tissue differentiation. This involves continual exchange of information among the cells and leads to (1) cell displacements and rearrangements, particularly during organogenesis and (2) extreme diversification of cell individualities within tissues, particularly during postembryonic growth. A mutation (just as a teratogenic factor) evokes an anomaly that is localized in both space and time because it alters a certain aspect of cell behaviour (particularly cell surface adhesiveness or mitotic activity) at the time when this is involved in the establishment of a particular structural trait. Neither the organization of the adult nor the modalities of development are encoded in the DNA. The automatic concatenation of cell interactions in the embryo and the structural amplification it entails is conditioned by the specific biochemical composition of the cytoplasm of the egg and by the heterogeneous distribution of its inclusions. (shrink)

Embryonic and adult field do not exhibit the same properties because they are formed by cell populations whose activities cannot be compared in all respects. Dominant cells are not distributed in the same manner; the same mechanisms are not involved for remodelling of the field, especially after an amputation.In adult organisms, cell equilibrium is disturbed a first time by elimination of differentiated tissues which provokes dedifferentiation and proliferation, and a second time by healing, which restores cell equilibrium of a distal (...) end. Undifferentiated cells begin to differentiate immediately after their production and they reform the missing levels, following a sequence either basipetal or basifugal according to the place of their production . The differentiating regenerate temporarily exhibits embryonic field properties in various experimental conditions which suppress the dominance of the stump or supplies additional undifferentiated material. (shrink)

The principles of automation in animal development, as previously inferred from the concept of Cell Sociology do not fit in well with the current concept of sequential gene derepression. A more adequate explanation for those principles has been found in the literature dealing with the biochemical aspects of differentiation. Since oocytes and embryonic cells contain a greater variety of mRNAs than differentiated cells, as well as many tissue-specific (luxury) substances, it is concluded that the diversification of tissues consists of a (...) progressive selection of specific metabolic strategies, mediated by cell-to-cell contacts, from a broad range of pre-existing strategies. For each tissue, prior to its final determination, one luxury metabolic strategy is progressively intensified and becomes dominant. The others are either suppressed or maintained as latent metabolic strategies. The latter may on occasion become dominant again (transdifferentiation). These phenomena require a theory which considers gene regulation as the activation of otherwise repressed genes by specific activator RNAs. The high (apparently maximal) transcriptional activity on the lampbrush chromosomes may represent the synthesis of all the kinds of activator RNAs which are required for the reactivation of the genes during early development. A general conception is propounded of the automatism and programming of animal development, as inferred from the confrontation of these ideas with the concept of Cell Sociology. (shrink)