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Following pioneering work by Harrison on amphibian limbs in the 1920s and by Saunders (1948) on the apical ridge in chick limbs, limb development became a classical model system for investigating such fundamental developmental issues as tissue interactions and induction, and the control of pattern formation. Earlier international conferences, at Grenoble 1972, Glasgow 1976,and Storrs, Connecticut 1982, reflected the interests and technology of their time. Grenoble was concerned with ectoderm-mesenchyme interaction, but by the time of the Glasgow meeting, the zone of polarizing activity (ZPA) and its role in control of patterning was the dominant theme. Storrs produced the first intimations that the ZPA could be mimicked by retinoic acid (RA), but the diversity of extracellular masrix ~olecules,particularly in skeletogenesis,was the main focus of attention. By 1990, the paradigms had again shifted. Originally, the planners of the ARW saw retinoic acid (as a possible morphogen controlling skeletal patterning), the variety of extracellular matrix components and their roles, and the developmental basis of limb evolution as the leading contemporary topics. However, as planning proceeded, it was clear that the new results emerging from the use of homeobox gene probes (first developed to investigate the genetic control of patterning of Drosophila embryos) to analyse the localised expression of "patterning genes" in limb buds would also be an important theme.
Scientific Frontiers in Developmental Toxicology and Risk Assessment reviews advances made during the last 10-15 years in fields such as developmental biology, molecular biology, and genetics. It describes a novel approach for how these advances might be used in combination with existing methodologies to further the understanding of mechanisms of developmental toxicity, to improve the assessment of chemicals for their ability to cause developmental toxicity, and to improve risk assessment for developmental defects. For example, based on the recent advances, even the smallest, simplest laboratory animals such as the fruit fly, roundworm, and zebrafish might be able to serve as developmental toxicological models for human biological systems. Use of such organisms might allow for rapid and inexpensive testing of large numbers of chemicals for their potential to cause developmental toxicity; presently, there are little or no developmental toxicity data available for the majority of natural and manufactured chemicals in use. This new approach to developmental toxicology and risk assessment will require simultaneous research on several fronts by experts from multiple scientific disciplines, including developmental toxicologists, developmental biologists, geneticists, epidemiologists, and biostatisticians.
In this book, the clinical chapters are organized into sections by defined developmental pathways or gene families, and each section is preceded by a general overview. For each disorder the authors cover the disease-causing genes, the role of these genes in development as elucidated in model organisms, the human mutations that have been identified, and the developmental pathogenesis of the condition. Clinical descriptions, along with discussions of therapy and counseling, are provided. This book will be an invaluable resource for physicians, dentists, and other health professionals and for basic scientists interested in developmental processes and genetic perturbations that affect them.
The embryonic development of the limbs is widely used as a paradigm for the comprehension of the cellular processes and molecular mechanisms underlying organogenesis and pattern formation. The chick, mouse and (recently), zebrafish embryos are excellent models, for the ease of experimental manipulation and the availability of several mutant strains with limb malformation defects.
'Patterning in Vertebrate Development' is a new volume in the 'Frontiers in Molecular Biology' series which provides a range of comprehensive, and authoritative reviews of current research into patterning, a fundamental process in developmental biology.