Factors Influencing Mammalian Kidney Development: Implications for Health in Adult Life (Advances in Anatomy, Embryology and Cell Biology Book 196)

In this monograph the authors have emphasized a number of important concepts in mammalian kidney development. Emphasis has been put on methodology so that the reader can understand how certain results or conclusions were reached and what the optimal methods for reliable results to be obtained are. In addition, as well as descriptions of the morphology there is information on the genetic basis of the structural development. In addition much attention has been paid to how nephron number may be altered by changes in the environment of the developing kidney and to the consequences for the remaining nephron gene expression and kidney function when total nephron number is altered. The consequences for the health of the adult, upon the formation of an adult kidney with altered nephron number and (potentially) gene expression, can be quite serious. The epigenetic mechanisms by which such changes can occur are introduced as a very fertile field for future investigation. There are many reasons why it is timely to review the development of the mammalian kidney. Perhaps the most important of these is the increasing amount of evidence to demonstrate that factors which impinge on/alter the normal developmental processes of this organ can have lifelong consequences for the health of the adult. The 'Developmental Origins of Health and Adult Disease' (DOHaD) hypothesis, proposes that changes in the environment during the development of an organ or system, can have permanent deleterious effects leading to increased risk of cardiovascular and/or metabolic disease. The permanent metanephric kidney has been shown to be very vulnerable to such influences with many factors shown to alter both the permanent structure and the level of expression of important functional genes. Thus it is important to understand the precise timing of kidney development in terms of both structure and the genes involved at each stage. Such knowledge has been gained by significant advances in technology, which allow quantification of the number of nephrons by unbiased stereology, detections of both levels and site of gene expression, 'knock-out' and knock-in' of genes in animal (mainly mouse) models and by the ability to examine nephron development, in real time, in culture systems Front Matter....Pages i-vii Introduction....Pages 1-1 Morphological Development of the Mammalian Kidney....Pages 1-9 Genetic Regulation of Metanephric Development....Pages 9-16 Abnormalities of Renal Development in the Human....Pages 16-17 Methodology to Examine Kidney Development....Pages 18-26 Development of Function in the Fetus....Pages 27-32 Nephron Endowment....Pages 32-39 Developmental Programming of the Kidney....Pages 39-54 Future Directions....Pages 54-57 Back Matter....Pages 58-78