Generation and regeneration of sequence of structures during morphogenesis

Abstract

Models for the generation and repair of sequences of structures in space are proposed. One possibility consists of the mutual or sequential induction of locally exclusive states. The general properties of such an interaction are demonstrated by a system of two components which mutually activate each other: the partition of a field into two parts with good size regulation is possible. Symmetric double gradients or periodic patterns can be formed. In a two-dimensional field, this type of interaction permits the formation of “stripes” of high concentrations of the components. In an extension to more than two components, sequences of structures are formed which show intercalary or terminal regeneration. Relatively simple molecular interactions can lead to such patterns. In some biological cases, experimental evidence suggests that the first step in the formation of a sequence is the determination of one or both terminal elements, followed by sequential filling in of the missing structures. The latter process can be mediated by a general signal formed at the discontinuity. If some monotonically increasing physical parameter r (positional value) occurs in the natural sequence, a discontinuity in the r-concentration is formed at the location of the gap. This discontinuity can be converted into a local maximum and/or minimum, serving as a gap sensing signal and leading to the induction of the missing structures. The other extreme type of model posits that the determination consists solely of the response of cells to the local concentration of a morphogen. In such a positional information scheme, a sequence of structures can be elongated by marginal growth if a feedback of the achieved states of determination orto the morphogen gradient is assumed. This permits the successive increase of the maximum morphogen concentration during the outgrowth enabling the accretion of new structures. The similarities in and differences between such models are discussed. Intermediate forms of these “pure” types are presumably involved in the control of development and some examples are given. Possible application to the developmental control of insects are discussed, in particular to the phenomena of intercalary regeneration and the duplication of excessive parts, as well as to the promimo-distal organisation of the vertebrate limb. Computer simulations are provided which demonstrate the feasibility of the models proposed.