Key Features
* Hundreds of color figures depicting key events in all aspects of kidney development
* Full coverage of the genetic and cellular basis of kidney development
* Analysis of the genetic basis of the major congenital kidney diseases
Organogenesis of the kidney has been intensely studied for over a century. In recent years advances in molecular techniques have not only made great inroads into exploring the genetic regulation of this complex process but also began to unravel the molecular basis of many forms of congenital kidney disease. This book is a comprehensive study on these findings and the only book available with such in depth coverage of the kidney. Hundreds of color figures depicting key events in all aspects of kidney development Full coverage of the genetic and cellular basis of kidney development Analysis of the genetic basis of the major congenital kidney diseases
Front Cover 1
The Kidney: From Normal Development to Congenital Disease 4
Copyright Page 5
Contents 6
Contributors 10
Foreword 12
Preface 14
Section I: Embryonic Kidneys and Models 16
Chapter 1. Introduction: Embryonic Kidneys and Other Nephrogenic Models 16
Chapter 2. Development of Malpighian Tubules in Drosophila Melanogaster 22
I. Introduction 22
II. Tubule Development and the Genes That Regulate It 24
III. Generating Cells: Regulation of Cell Proliferation in the Tubule Primordia 26
IV. Morphogenetic Movements 28
V. Onset of Physiological Activity 29
Chapter 3. Induction, Development, and Physiology of the Pronephric Tubules 34
I. Introduction 34
II. Tubule Fate and Origins 34
III. Pronephric Induction 38
IV. Pronephric Tubule Anatomy 44
V. Morphogenesis 53
VI. Pronephric Function and Physiology 57
VII. Degeneration or Function Diversion of the Pronephros 61
VIII. Pronephric Tubules as a Model for Tubulogenesis? 62
Chapter 4. Formation of the Nephric Duct 66
I. Introduction 66
II. Nephric Duct Morphogenesis 67
III. Conclusions 73
References 74
Chapter 5. The Pronephric Glomus and Vasculature 76
I. Introduction 76
II. Development of the Pronephric Glomus: Stages of Glomerular Development in Frogs and Fish 81
III. Gene Expression and Function in Pronephric Glomerular Development 84
IV. Summary: Future Prospects 86
Chapter 6. Development of the Mesonephric Kidney 90
I. Introduction 90
II. Mesonephric Development: An Anatomical Overview 90
III. Molecular Basis of Mesonephric Development 94
IV. Mesonephric Contribution to Gonadal Differentiation 96
V. Mesonephric Contribution to Other Organ Systems 98
VI. Summary 99
References 99
Chapter 7. Three-Dimensional Anatomy of Mammalian Mesonephroi 102
I. Introduction 102
II. Material 102
III. Three-Dimensional Reconstruction 103
IV. Human Mesonephric Development 103
V. Murine Mesonephric Development 104
VI. Conclusions 105
References 107
Chapter 8. Molecular Control of Pronephric Development: An Overview 108
I. Introduction 108
II. Transcription Factors Implicated in Development of the Pronephros 109
III. Growth Factors in Pronephric Kidney Development 118
IV. Conclusions and Further Perspectives 124
Reference 128
Chapter 9. Embryological, Genetic, and Molecular Tools for Investigating Embryonic Kidney Development 134
I. Introduction 134
II. Molecular Embryology 134
III. Cellular Embryology 138
IV. Transgenic Methods 142
V. Classical Genetic Methods: Mutant Screens 144
References 148
Section II: The Adult Kidney 154
Chapter 10. The Metanephros 154
I. Introduction 154
II. Development of the Metanephros 154
III. Growth 158
IV. Investigating Regulatory Networks 160
V. Unsolved Problems of Kidney of Development 160
References 162
Chapter 11. Anatomy and Histology of the Human Urinary System 164
I. Gross Anatomy of the Urinary System 164
II. Microanatomy of the Urinary System 170
References 179
Chapter 12. Development of the Ureteric Bud 180
I. Introduction 180
II. Induction of Ureteric Bud Formation 182
III. Anatomy of Ureteric Bud Arborization 183
IV. Mechanisms of Ureteric Bud Arborization 184
V. Integration of Influences 188
VI. Engines of Morphological Change 189
VII. Differentiation within the Maturing Collecting Duct 190
VIII. Some Outstanding Problems 190
References 191
Chapter 13. Fates of the Metanephric Mesenchyme 196
I. Summary 196
II. Introduction 196
III. Early Stages of Kidney Formation 197
IV. Cell Types Derived from Metanephric Mesenchyme 198
V. Experimental Analysis of Metanephric Mesenchyme Differentation 202
VI. How Many Cell Types Are Present in the Metanephric Blastema? 204
References 206
Chapter 14. Formation and Development of Nephrons 210
I. Introduction 210
II. Morphogenesis 211
III. Induction 211
IV. Intrinsic Factors That Control the Induction Response 216
V. Factors That Drive Mesenchyme-to-Epithelial Conversion 218
VI. Summary 222
References 223
Chapter 15. Establishment of Polarity in Epithelial Cells of the Developing Nephron 226
I. Summary 226
II. Introduction 226
III. Acquisition of Epithelial Polarity 227
IV. Structural Organization 227
V. Physiological and Biochemical Organization 229
VI. Establishment and Maintenance of Epithelial Cell Polarity 230
VII. Protein Trafficking in Embryonic Kidney 233
VIII. A Final Comment 234
References 234
Chapter 16. Development of the Glomerular Capillary and Its Basement Membrane 236
I. Introduction 236
II. Glomerular Structure 236
III. Glomerular Filtration Barrier 238
IV. Glomerular Basement Membrane Proteins 239
V. Unique Features of Podocytes 243
VI. Glomerulogenesis 245
VII. Glomerular Defects 256
VIII. Closing Remarks 258
References 258
Chapter 17. Development of Kidney Blood Vessels 266
I. Introduction 266
II. Blood Vessel Formation in the Embryo 267
III. Anatomy of Kidney Blood Vessels 267
IV. Experiments that Address the Origins of Metanephric Blood Vessels 271
V. Growth Factor and Embryonic Kidney Vessel Development 274
VI. Other Molecules Involved in Vascular Growth 277
VII. Conclusions and Perspectives 278
References 278
Chapter 18. Development of Function in the Metanephric Kidney 282
I. Introduction 282
II. Methods to Study Developmental Renal Physiology 283
III. Development and Regulation of Renal Blood Flow 284
IV. Development and Regulation of Glomerular Filtration 291
V. Ontogeny of Tubular Function 293
VI. Summary 320
References 321
Chapter 19. Experimental Methods for Studying Urogenital Development 342
I. Introduction 342
II. Tissue Dissection and Separation 342
III. Culturing Metanephric Kidney Rudiments 345
IV. Tissue Analysis 349
V. In Situ Hybridization of mRNA 350
References 357
Chapter 20. Overview: The Molecular Basis of Kidney Development 358
I. Introduction 358
II. Specification of Nephrogenic Mesenchyme 358
III. Cell Survival 362
IV. Mesenchymal Condensation 368
V. Proliferation 369
VI. Branching of the Ureteric Bud 371
VII. Mesenchyme-to-Epithelial Transition 376
VIII. Proximal/Distal Patterning 380
IX. Glomerulogenesis 380
X. Vascularization 383
XI. Cell Polarity 383
XII. Future of the Field 384
References 385
Section III: Congenital Disease 392
Chapter 21. Maldevelopment of the Human Kidney and Lower Urinary Tract: An Overview 392
I. Normal Development of Human Kidney and Lower Urinary Tract 392
II. Varied Phenotypes of Human Kidney and Lower Urinary Tract Maldevelopment 396
III. Causes of Maldevelopment of Human Kidney and Lower Urinary Tract 398
References 403
Chapter 22. WT1-Associated Disorders 410
I. Introduction 410
II. The WT1 Gene 411
III. WT1 and Development 412
IV. WT1 and Wilms’ Tumor 413
V. WT1 and Other Malignancies 415
VI. WT1and Denys–Drash Syndrome 415
VII. WT1 and Isolated Diffuse Mesangial Sclerosis 417
VIII. WT1 and Frasier Syndrome 418
IX. WT1 Intronic Mutation (Frasier Mutation) in 46,XX Females and in Primary Steroid–Resistant Nephrotic Syndrome 419
X. Conclusions 420
References 421
Chapter 23. PAX2 and Renal-Coloboma Syndrome 426
I. Introduction 426
II. Pathologic Analysis of Renal-Coloboma Syndrome and Oligomeganephronia 427
III. Molecular Analysis of the PAX2 Gene and Its Involvement in Renal-Coloboma Syndrome 431
IV. Animal Models to Investigate PAX2 Function 439
V. What Is the Function of PAX2 in Kidney Development? 442
VI. Summary 443
References 444
Chapter 24. Cystic Renal Diseases 448
I. Human Clinical Disease Impact 448
II. Molecular Genetics of Human Renal Cystic Diseases 451
III. Animal Models and the Pathogenesis of Polycystic Kidney Diseases 456
IV. General Mechanisms Underlying Cystogenesis and the Function of Proteins Causing Polycystic Kidney Disease 459
V. Summary 460
References 460
Chapter 25. Renal Cell Carcinoma: The Human Disease 466
I. Phenotypic Diversity of Renal Cell Carcinoma (RCC) 467
II. Molecular Genetics of RCC 467
III. The von Hippel–Lindau Tumor Suppressor Gene 468
IV. TSC-2 Tumor Suppressor Gene 469
V. c-met 470
VI. Other Genes Involved in RCC 470
VII. Animal Models for RCC 471
References 472
Chapter 26. The Tubule 476
I. Introduction 476
II. Proximal Tubulopathies 477
III. Defects of the Thick Ascending Limb and Distal Tubule 481
IV. Disorders of the Amiloride-Sensitive Epithelial Sodium Channel 484
V. Disorders of the Collecting Dust 484
VI. Conclusions 485
References 485
Chapter 27. Diseases of the Glomerular Filtration Barrier: Alport Syndrome and Congenital Nephrosis (NPHS1) 490
I. Alport Syndrome 491
II. Congenital Nephrosis NPHS1 495
III. Conclusions 497
References 498
Chapter 28. Congenital Kidney Diseases: Prospects for New Therapies 502
I. Introduction 502
II. Gene Transfer Technologies 502
III. Renal Precursor Cell Technology 504
IV. Experimental Treatments for Polycystic Kidney Diseases 505
References 505
Index 508
1 Introduction: Embryonic Kidneys and Other Nephrogenic Models
Peter D. Vize
I am a reformed lover of mesoderm induction. My association with the pronephros began for opportunistic reasons with the original plan being to exploit the expression of pronephric genes as markers of the patterning and establishment of the intermediate mesoderm. However, after finding such markers and following their expression in forming pronephroi, I became more interested in how these genes contributed to the regulation of kidney morphogenesis than in simply using them as markers of earlier events. Upon exploring what was known about embryonic kidney development (very little) and what could be learned using modern molecular embryology (an enormous amount), my future research directions were established. The embryonic kidneys are an ideal system in which to explore cell signaling, specification, adhesion, shape change, morphogenesis, and of course organogenesis. In addition to being a wonderful intellectual problem, the analysis of embryonic kidney development has many advantages in terms of the availability of techniques with which to dissect the process. Some of the organisms with the most extensive and well developed embryonic kidneys are also those with the most highly advanced genetic and embryological tools—a perfect match. Finally, similar genetic networks regulate the development of all nephric organs so data gleaned from embryonic systems are as relevant to human congenital disease as they are to the understanding of a quaint model.
This first section of “The Kidney” covers the development of the embryonic kidneys, the pro- and mesonephroi, in a depth never before attempted in a text on kidney development and function. For those who no longer recall their undergraduate developmental biology course, even the names of these organs may be unfamiliar. After all, some mammals (including humans) can survive until birth without any kidneys, so of what interest are transient organs that some would posit are nothing more than evolutionary artifacts? In this introduction some of the reasons for refraining from such an opinion will be explored, as will the renaissance of research into the use of embryonic kidneys as model systems for the analysis of organogenesis. The following chapters provide a detailed description of the anatomy, development, function, and molecular biology of the transient embryonic kidneys as a resource for those willing to accept my arguments regarding relevancy. Similar arguments can be made supporting the relevance of invertebrate models of nephrogenesis, and Chapter 2 opens with a review of Malpighian tubule morphogenesis in the fruit fly, Drosophila melanogaster.
The embryonic kidney of amphibians and fish is known as the pronephros, head kidney, or vorniere, while their adult kidney is known as a mesonephros, Wolffian body, or urniere. In some instances, fish and frog permanent mesonephroi are unnecessarily referred to as opisthonephroi, a term used to distinguish them from the transient mesonephroi of amniotes, but which results in more confusion than clarification. To begin the description of the development of vertebrate embryonic kidneys, a brief description of the occurrence of pro- and mesonephroi is appropriate. All vertebrates have distinct embryonic and adult kidneys (Goodrich, 1930; Burns, 1955; Saxén, 1987). Upon development of the adult kidney, the embryonic kidney usually either degenerates or becomes a part of the male reproductive system (Burns, 1955; Balinsky, 1970). In some instances the embryonic kidney switches to a new role as a lymphoid organ (Balfour, 1882).
Well-developed, functional pronephroi are found in all fish, including dipnoids (e.g., lungfish), ganoids (e.g., sturgeon), and teleosts (e.g., zebrafish), and in all amphibians. Reptiles vary in the degree to which pronephroi form, with the more primitive reptiles having the most advanced pronephroi (Chapter 3). Birds have only a poorly developed pronephros, as do most mammals. In organisms with aquatic larvae, pronephroi are absolutely essential for survival. The pronephroi excrete copious amounts of dilute urine that allows such animals to maintain water balance. If the pronephroi are not functional, aquatic larvae die rapidly from oedema (Chapter 3).
Pronephric kidneys are very simple and form within a day or two of fertilization. They usually contain a single nephron with an external glomerulus or glomus (Fig. 1.1). This glomus filters blood in an identical manner to standard glomeruli, except that the filtrate is deposited into a cavity rather than into Bowman’s space. In some instances, this cavity is the coelom, in others, a dorsal subcompartment of the coelom known as the nephrocoel, and in yet others into the pericardial cavity. The glomeral filtrate is collected from the receptive cavity by ciliated tubules known as nephrostomes. The nephrostomes in turn are linked to the pronephric tubules. These tubules have distinct proximal and distal segments. As with a classical mammalian nephron, the proximal segment functions in solute resorption and waste excretion, whereas the distal segment resorbs water. From the distal tubule urine passes down the pronephric duct to the cloaca. The entire pronephros is in essence a single large nephron. This section uses the term pronephros to describe an embryonic kidney that either utilizes an external glomus or is anatomically distinct from the mesonephric kidney in the same organism. Details of pronephric anatomy and complete bibliographies are provided by Chapters 3 through 5.
Figure 1.1 Embryonic kidney nephrons. (Left) Lateral and anterior views of a frog pronephric nephron at around the onset of function are illustrated. The anterior border of the distal tubule is marked in the lateral view. The posterior border of this segment has not yet been defined, but the transition region is indicated. (Right) Two common forms of mesonephric nephron are illustrated. In each case, a glomerulus projects into the tip of the proximal segment. In the upper example the nephron branches into a peritoneal funnel that links the proximal tubule to the coelom. This type of nephron receives fluids from two sources: the glomerulus via filtration and the coelom via ciliary action (Chapter 3). ns1, ns2, ns3, nephrostomes 1 through 3; db1, db2, db3; dorsal branches 1 through 3; cmn, common (or broad) tubule; dstl, distal tubule; duct, nephric duct; p/d border, border between proximal and distal tubule zones; va, vas afferens; ve, vas efferens.
Mesonephric kidneys are more complex in organization and consist of a linear sequence of nephrons (Fig. 1.2) linked to the nephric duct (Fig. 1.1). Mesonephric nephrons contain internal (or integrated) glomeruli, and in some instances, particularly in anterior mesonephric tubules, also link to the coelom via ciliated tubules called peritoneal funnels. Such funnels are sometimes referred to as nephrostomes, which they resemble very closely, but the correct nomenclature of the two structures allows one to specify whether the funnel links the coelom to the glomerulus or the glomerulus to the tubule. Nephrostomes are also sometimes present in mesonephroi so the distinction is important.
Figure 1.2 Transition between pro- and mesonephroi in the frog, Rana temporaria, ventral view (after Marshall, 1902). The arterial system is colored red, the venous system blue, and the pronephric glomus (GM) purple. Pronephric (P) and mesonephric (MS) tubules are in green and the nephric duct (PND) is in yellow. Tadpoles of 6.5 mm (A), 12 mm (B), 40 mm (C), and a metamorph (D). Additional labeled structures correspond to A, dorsal aorta; AF, afferent branchial vessels; AL, lingual artery; AP, pulmonary artery; AR, anterior cerebral artery, CA, anterior commissural artery; CG, carotid gland; CP, posterior commissural artery, EF, efferent branchial vessels; EH, efferent hyoidean vessel; EM, efferent mandibular vessel, GE, gill; GM, glomus; KS, nephrostome; KU, ureter; MS, mesonephros/mesonephric tubules; OR, genital ridge; PND, nephric duct; P, pronephros; KS, nephrostomes; RT, truncus arteriosus; RS, sinus venosus, RV, ventricle; TC, cloaca; TO, oesophagus, cut short; TR, rectal sprout.
The mesonephros is first functional at around 7.5 days of development in the frog Xenopus (Nieuwkoop and Faber, 1994) and continues to grow along with the animal. In organisms in which the mesonephros is transient, the complexity of this organ is extremely variable, ranging from almost no nephrons in rodents to 34 in humans and 80 in pigs (Felix, 1912; Bremer, 1916; Table 1.1). The anatomy of a human mesonephros is illustrated in Fig. 1.3.
Table 1.1 The Mesonephric Nephron Number
Figure 1.3 Human mesonephros (9.5 mm). Anterior nephrons are undergoing degeneration. Each nephron has an S-shaped tubule linking the glomerulus to the nephric duct. There is some variation in the spacing of the mesonephric tubules, and some glomeruli share a common collecting duct (e.g., glomeruli 15 and 16 and glomeruli 19 and 20 in the left mesonephros).
After Felix (1912).
In animals in which the mesonephros is the terminal kidney, such as amphibians and fish, the final organ is very complex, containing a large number of nephrons, most of which have an internal glomerulus. In the example of the frog...
| Erscheint lt. Verlag | 14.3.2003 |
|---|---|
| Sprache | englisch |
| Themenwelt | Medizinische Fachgebiete ► Innere Medizin ► Nephrologie |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Urologie | |
| Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie | |
| Naturwissenschaften ► Biologie ► Humanbiologie | |
| Technik | |
| ISBN-10 | 0-08-052154-1 / 0080521541 |
| ISBN-13 | 978-0-08-052154-1 / 9780080521541 |
| Haben Sie eine Frage zum Produkt? |
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