Innate chaos: I. The origin and genesis of complex morphologies and homeotic regulation.
The genesis of complex morphologies is an inherent property of all dynamically expanding natural systems. In the inorganic and prebiotic world, chaotic movement of quantitable particles results in formation of ordered streamlined structures or micelles close to phase boundaries. In the course of chemical and colloid crystallization or development of living organisms, complex morphologies emerge, due to unusual chaotic attraction, diffusion limited aggregation (DLA) and multifractal organization suggesting that common mechanisms direct the morphogenesis in a wide range of natural systems. The development of a multicellular organism from a single fertilized oocyte requires intensive clonal proliferation sequential determinations and the organization of terminally differentiated cells in morphologically stable homeostatic functional units. Comparative data on insect and vertebrate embryogenesis revealed that the spatial organization of the developing body is orchestrated by several mechanisms: maternal effect genes or cell position specify the initial polarities and the main axes, while metameric segmentation, intrasegment identity and cell fate are determined by the programmed expression of morphogenetic determinants. They include evolutionarily conserved DNA binding proteins containing homeobox or pair-box sequences, endogenous ligands, activating specific nuclear hormone receptors, and humoral growth factors acting via specific membrane receptors and more ubiquitous transducing pathways. Morphogenetic regulators form intratissual gradients and demark fields required for the correct realization of the developmental programme. It has been recognized that the cell's freedom is limited to stringent developmental choices that in the end results in the formation of coherent cell colonies, many of them displaying chaotic behaviour. The linkage between embryonic regulation and adult tissue differentiation is not completely elucidated, however, data are emerging to show that several morphogenetic regulators may function throughout life in different human tissues. Genetically transmissible deletions or acquired impairments likely contribute to malignant tissue growth. Diffusible morphogenetic regulators may reverse the malignant phenotype in some cases and induce clinical remission. Further work is needed, however, to identify the dominant components of physiological regulatory networks and to understand what hierarchical organization and chaotic behaviour represent in order to elaborate new combined therapeutic protocols.
Blazsek
I
I
Institut du Cancer et d'Immunogénétique Université Paris-Sud, Association Claude Bernard et ARC, Hôpital Paul Brousse, Villejuif, France.
D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000382:microbiology; D006801:Humans; D009024:Morphogenesis