ULAR INTERACTION DURING DIFFERENTIATION

Summary There are two opposed ideas as to the nature of cellular interaction during differentiation and development of pattern. The hypothesis of specific induction was derived from studies in which a graft caused a large area of a host to transform and develop in conformity with the graft. The belief grew that the graft released inductors which specifically directed the differentiation of the recipient cells. More recently, after many years of failure in the quest for specific inductors and because cellular contact was necessary for interaction, the amendment that pattern spreads as the result of contact-induced surface changes was proposed. Before and during the growth of the concept of specific induction the hypothesis of specific inhibition was being elaborated. According to this view, pattern arises as the products of differentiating regions act on other areas and suppress like differentiation there. The dominated areas, prevented from developing as they would have done in isolation, are reduced to a lower order of differentiation. These in turn suppress like differentiation in other cells and thus allow a still less efficient reaction to succeed. Thus, by a series of inhibitions, differences could arise. Most of the early experiments upon which specific inhibition theory was built were made with plants, but some experiments with animal embryos and regenerates were interpreted in the same way. Many experiments indicating the unspecific nature of induction with tissues and extracts have gradually led to a belief in a more general type of induction. At the same time the quest for specific inductors continues, but recent experiments purporting to show specific induction may be interpreted otherwise. hypothesis of general induction plus specific inhibition seems to account for a number of experimental results obtained from studies of eyes, combinations of the mesodermal mantle and xenoplastic transplantations, all in the Amphibia. This view also accounts for the fact that in many cases of regeneration it is known that a particular organ can develop from a variety of tissue sources, as is well known for plants. Cases of multiple pathway development, in which organs arise from different tissue sources under various experimental conditions, are cited from five animal phyla. These facts speak strongly against any system of differentiation and pattern formation in which pattern is entirely dependent upon past history. Instead we learn that in many parts of numerous organisms a great variety of tissues will regulate to form missing structures. Apparently ability to differentiate is not lost as the result of differentiation. Organization is maintained as already formed structures suppress like differentiation in potentially like tissues. The opposed view of irreversible differentiation is considered and found inadequate. The theoretical need for it no longer exists. In the days when differentiation was believed to occur by segregation a belief in irreversible differentiation was also necessary. If cells differentiated and lost the ability to develop along other pathways they were irreversibly differentiated. The observations that tissues and organs did transform from one well-differentiated type to another, if the belief in irreversible differentiation was still held, made it necessary to assume that there remain in differentiated tissues some undifferentiated reserve cells. Detailed studies of transformations in animals and in plants demonstrate that changes from one tissue to others may occur without reserve cells. Even though there is no longer a theoretical need for irreversible differentiation and reserve cells, it is still possible that les differentiated cells do act as a reservoir which is drawn upon during regeneration. It has not yet been demonstrated, however, that any reserve cell has throughout its history remained undifferentiated. The so-called reserve cells of coelenterates and flatworms may be transition stages in the transformation from cells of one tissue type to those of another. Various experiments not covered by specific induction theory but which are interpretable as specific inhibitions are reviewed, including specific inhibitions by extracts in plants and animals. It has long been considered that some integrating factor in addition to direct cellular interaction must be responsible for organization. It is proposed here that this factor is polarity and that, again as demonstrated for plants, patterns of organization arise as specific inhibitors move in polarized fields. Recent data from studies of regenerating Tubularia indicate that grafts induce secondary structures, but further analysis shows that they induce a new polarity and that along the new polarized route every level can become the most anterior stucture not already developing upstream from it. It is also suggested that embryonic induction may operate in the same way. Points of disagreement with segregation, competition and template-antitemplate theories are discussed.