| List of Contents | 6 |
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| Abstract | 9 |
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| 1 Introduction | 10 |
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| 2 Morphological Development of the Mammalian Kidney | 10 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 9.1 Clock Genes | 64 |
| 9.2 Renal Stem Cells and Renal Regeneration | 65 |
| 9.3 New Renal Factors | 65 |
| References | 67 |
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| Subject Index | 88 |