Factors Influencing Mammalian Kidney Development: Implications for Health in Adult Life (eBook)

List of Contents 6
Abstract 9
1 Introduction 10
2 Morphological Development of the Mammalian Kidney 10
2.1 Pronephros 12
2.2 Mesonephros 12
2.3 Metanephros 14
2.4 Renal Vascular Development 16
2.5 Development of the Renal Nerves 18
3 Genetic Regulation of Metanephric Development 18
3.1 Molecular Specification of the Metanephric Blastema 19
3.2 Molecular Regulation of Ureteric Budding and Branching Morphogenesis 19
3.3 Molecular Regulation of Nephrogenesis 21
3.4 Molecular Regulation of the Stroma 23
3.5 The Renin–Angiotensin System: An Important System Regulating Renal Development and Function 23
3.6 Summary of Molecular Regulation of Metanephric Development 24
4 Abnormalities of Renal Development in the Human 25
4.1 Hydronephrosis 25
4.2 Congenital Anomalies of the Kidney and Urinary Tract 25
4.3 Bilateral Renal Agenesis (Potter's Syndrome) 26
4.4 Renal Abnormalities Caused by Maternal Drug Use 26
4.5 Polycystic Kidney Disease 26
5 Methodology to Examine Kidney Development 27
5.1 Organ Culture 27
5.2 Three-Dimensional and Four-Dimensional Imaging 29
5.3 Quantitation of Nephron Number 30
5.4 Microarrays 33
5.5 Use of Knock-in/Reporter Mice to Analyse Gene Function and Expression 34
6 Development of Function in the Fetus 36
6.1 Mesonephric Function 36
6.2 Fetal Metanephric Renal Function 36
6.3 Sodium Transporters 37
6.4 Water Channels 41
6.5 Renal Renin–Angiotensin System 41
7 Nephron Endowment 41
7.1 Nephron Endowment in the Human 41
7.2 Effect of Prematurity 44
7.3 Factors Important for Normal Kidney Development 45
7.3.2 Iron 45
7.4 Timing of Nephrogenesis and Nephron Endowment in Animal Models 46
8 Developmental Programming of the Kidney 48
8.1 Overview: The Developmental Origins of Health and Disease Hypothesis 48
8.2 Human Epidemiology 49
8.3 Common Animal Models Used to Test the DOHaD Hypothesis 50
8.4 Reduced Nephron Endowment: A Common Denominator in the DOHaD Hypothesis? 52
8.5 Link Between Nephron Endowment and Hypertension 55
8.6 Mechanisms Leading to a Reduced Nephron Endowment 56
8.7 Programmed Changes in Renal Gene Expression 57
8.7.2 Sodium Channels 57
8.8 Why a Low Nephron Endowment Does Not Always Lead to Hypertension 58
8.9 Unilateral Nephrectomy as a Model of Low Nephron Endowment 62
8.10 Potential Underlying Mechanisms of Developmental Programming 62
9 Future Directions 63
9.1 Clock Genes 64
9.2 Renal Stem Cells and Renal Regeneration 65
9.3 New Renal Factors 65
References 67
Subject Index 88