On the Generation of Form by the Continuous Interactions Between Cells and Their Extracellular Matrix

The central issue of this essay is the problem of how multicellular organisms develop and maintain the complex architecture and intricate shape of tissues and organs. The concepts pattern formation, morphogenesis and differentiation are defined and discussed suggesting a distinction between processes that underlie uniformity (e.g. basic body plans) and those underlying inter- and intra-species variation. The initial stage of limb bone development--the formation of the mesenchymal condensation--is described in detail. On the basis of these data and many additional example from other developmental systems, the central role of continuous cell-ECM interactions in the generation of form is deduced. Evidence is provided as to the leading role of the mesenchymal-fibroblast-like cells in sculpturing tissue and organ architecture. It is proposed that a group of cells within their ECM, rather than the single cell, is the functional unit relevant to the generation of form. The continuous cell-ECM interactions lead to the generation of form not by a detailed obligate pathway, but rather by a process of 'selective stabilization' (Kirschner & Mitchison, 1986), i.e. a gradual organization into more stable structures, where existing structural configuration serve to increase the likelihood of certain configurations and reduce that of others. Data are quoted to support the notion that even cell division does not erase all the structural information imprinted in the cell. The role of the metazoan genome in morphogenesis is discussed in the light of the process of selective stabilization.