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This section of notes introduce nephron and glomerular development. The specialized structures within the kidney involved with filtering the blood, reabsorbtion, secretion, and generation of urine are called nephrons. In the normal adult human kidneys ranges from 300,000 to more than 1 million. These nephrons are mainly generated in the fetal stage of development and we are born with all the nephrons we will have throughout our life. In one study, mean glomerular number was shown to level at 36 weeks, increasing from about 15,000 at 15 weeks to 740,000 at 40 weeks. In other species, rat nephron generation (nephrogenesis) occurs mainly in the first week or so postnatally and fetal sheep have been used in many studies on the development of the kidney. |
Adult Nephron Structure (Image: Blue Histology) |
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Page Links: Introduction | Some Recent Findings | Development Overview | Nephron Mophology | Fetal Kidney | Nephron Histology | Computer Activities | Glossary | References
Related Pages: Abnormalities | References | Stage13/14 | Stage 22 | Selected Human highpower | WWW Links
Quaggin SE, Kreidberg JA. Development of the renal glomerulus: good neighbors and good fences. Development. 2008 Feb;135(4):609-20. Epub 2008 Jan 9. Review.
"Recent studies have changed our conception of the glomerulus from a relatively static structure to a dynamic one, whose integrity depends on signaling between the three major cell lineages: podocytes, endothelial and mesangial cells."
Costantini F. Renal branching morphogenesis: concepts, questions, and recent advances. Differentiation. 2006 Sep;74(7):402-21.
Ureteric Bud (UB) forms from mesonephric (Wolffian duct) and begins growing toward metanephric mesenchyme.
Ureteric Bud elongates and comes into contact with loose metanephric mesenchyme and condenses.
Ureteric Bud branches to form collecting ducts and condensed metanephric mesenchyme undergoes an epithelial transformation and forms comma and S-shaped bodies.
Nephron Unit includes glomerulus and proximal tubule, forms from comma and S-shaped bodies.
Early Fetal Kidney (Week 10) |
Humans Glomerular number appears to level by the end of the fetal period 36 weeks
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| Vascular and Urinary Poles of the Glomerulus | |
| Adult Glomerulus Structure (Images: Blue Histology) |
UNSW Embryology: 2008 Science ANAT2341 - Embryology Lecture - Kidney Development |
Kidney Notes Pages: Abnormalities | References | Stage13/14 | Stage 22 | Selected Human highpower | Genital | Genital Abnormalities | Urogenital Text only page | WWW Links | Molecular | References
Human Embryology Movies: Cervical Nephrotomes, Mesonephros and Metanephros (553Kb) | Development of the Renal Collecting System (298Kb) | Movies
Embryo Images Unit: Embryo Images Online | Urongenital Development | Primitive Kidney |
Reviews
Quaggin SE, Kreidberg JA. Development of the renal glomerulus: good neighbors and good fences. Development. 2008 Feb;135(4):609-20. Epub 2008 Jan 9. Review.
Articles
Skinner MA, Safford SD, Reeves JG, Jackson ME, Freemerman AJ. Renal Aplasia in Humans Is Associated with RET Mutations. Am J Hum Genet. 2008 Feb;82(2):344-51.
Nyengaard JR, Bendtsen TF. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec 1992 Feb;232(2):194-201
"The number and size of glomeruli in normal, mature human kidneys were estimated by a direct and unbiased stereological method, the fractionator. The number was 617,000 on average, and the mean size 6.0 M cubic microns. Both glomerular number and size showed significant negative correlation to age and significant positive correlation to kidney weight. Apparently, humans loose glomeruli with age. Body surface area correlated positively to kidney weight and total glomerular volume but not to number of glomeruli. ...Thus, intraspecies adaptation of kidney filtration capacity to the metabolic demand is performed by changing the size of glomeruli, i.e., the number of glomeruli in individuals of a given species is independent of the metabolic rate."
Vainio SJ, Uusitalo MS. A road to kidney tubules via the Wnt pathway. Pediatr Nephrol. 2000 Nov;15(1-2):151-6
"Classical in vitro studies indicate that tubule induction in the kidney mesenchyme is mediated by cell-cell contacts between the inducer tissue and the metanephric mesenchyme. Induction is completed within the first 24 h, after which tubules will form because of stimulated cell proliferation, migration, and cell adhesion. Recent evidence has revealed an essential role for the secreted signals from the Wnt gene family. Of these, Wnt-4 is expressed in developing tubules and knocking out its function perturbed kidney development. More detailed studies demonstrated normal condensation, but tubules were missing. Subsequent experiments indicated that Wnt-4 is also a sufficient signal to trigger tubulogenesis. Cells that were engineered to express Wnt-4 not only induced tubulogenesis in the kidney mesenchyme of Wnt-4 mutant embryos, but also induced tubules in the wild type mesenchyme. With the transfilter induction assay, Wnt-4-mediated induction was completed within the first 24 h, depending on the presence of proteoglycans and cell-cell contacts between the interactants. In addition, Wnt-4 autoinduced expression of its own gene and a panel of other components of the Wnt signalling pathway, such as frizzleds and a candidate Wnt antagonist from the secreted frizzled-related protein family. Taken together, the data provide evidence of an essential role for Wnt signal transmission and transduction pathways in the induction of kidney tubules, and the findings have paved the way for detailed molecular studies."
Schedl A, Hastie ND. Cross-talk in kidney development. Curr Opin Genet Dev. 2000 Oct;10(5):543-9.
"As in most organs, the emerging theme in kidney development is the importance of cross-talk between several tissues and cell lineages to allow morphogenesis to proceed in a complex but highly regulated way. Over the past few years, knock-out and transgenic analyses in mice and evolutionary comparison with non-mammalian species have been particularly instrumental in identifying molecules with crucial functions for tissue-tissue interactions. The transcription factors Wt1 and Eya1, the signalling molecules Gdnf and LIF and the receptors c-Ret and GdnfRalpha have been demonstrated to fulfil fundamental roles in the first step of metanephric induction, the outgrowth of the ureter. Signalling by members of the Wnt, BMP and FGF families, regulated by transcription factors such as Pax2, mediates nephrogenesis by adjusting the balance between the ureteric bud epithelium, stromal and nephrogenic tissues. The stromal tissue, neglected for many years, has been shown to serve important functions in regulating the growth of nephrons. Finally, we have also begun to gain insight into the molecular events underlying patterning of the nephron into distinct functional units including glomerulus, proximal and distal tubule."
Drummond IA. The zebrafish pronephros: a genetic system for studies of kidney development. Pediatr Nephrol. 2000 May;14(5):428-35.
"The zebrafish, as a model system for vertebrate development, offers distinct experimental advantages for studies of organogenesis. The simplicity of the zebrafish pronephros, the feasibility of isolating large numbers of mutants, and the growth in infrastructure for genomics makes the zebrafish an attractive system for the analysis of kidney development. Mutants affecting several aspects of nephrogenesis, including differentiation of the intermediate mesoderm, nephron patterning, epithelial polarity, and angiogenesis, have been isolated. Analysis of mutant phenotypes and the cloning of mutant genes has revealed: (1) a role for bone morphogenetic proteins in patterning the ventral mesoderm, (2) an essential role for the pax2.1 gene in pronephric development, (3) multiple loci required for establishing epithelial polarity in the pronephric duct, (4) a central role for podocytes in directing glomerulogenesis, and (5) 15 loci associated with cystic maldevelopment in the pronephros. The striking similarities of pronephric cell types to those found in higher vertebrates, as well as the conservation of kidney-specific gene expression patterns, suggest that insights gained from studies in zebrafish will be broadly applicable to cell differentiation in the kidney."
Lelievre-Pegorier M, Merlet-Benichou C. The number of nephrons in the mammalian kidney: environmental influences play a determining role. Exp Nephrol. 2000 Mar-Apr;8(2):63-5.
"Several lines of evidence, mostly derived from animal studies, indicate that changes in the fetal environment may affect the renal development. Fetal growth retardation is associated with a nephron deficit in both humans and animals. Changes in the supply of vitamin A to the fetus may be responsible for the variations in the number of nephrons in the human kidney. In utero exposure to hyperglycemia or drugs may also cause a nephron deficit."
Search PubMed Sep 2008 "glomerulus development" 3,196 reference articles of which 411 were reviews.
Search PubMed Now: glomerulus development | embryonic glomerulus development | podocyte development | glomerular endothelial development | mesangial cell development |
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bladder exstrophy - A congenital malformation with bladder open to ventral wall of abdomen (between umbilicus and pubic symphysis) and may have other anomolies associated with failure of closure of abdominal wall and bladder (epispadias, pubic bone anomolies).
blastema - Term used to describe a mass of undifferentiated cells. (More? Wilm's tumour)
diabetes insipidus - The disorder is related to the hormone antidiuretic hormone (ADH, also called vasopressin) its synthesis, secretion, receptors and signaling pathway. In diabetes insipidus there is an excretion of large amounts (up to 30 litres/day) of a watery urine and an unremitting thirst (More? Kidney Abnormalities - Diabetes Insipidus)
hydronephrosis - (congenital hydronephrosis, Greek, hydro = water) A kidney abnormality due to partial or complete obstruction at the pelvi-ureteric junction. This leads to a grossly dilated renal pelvis causing extensive renal damage before birth.
hyperplastic rests - In kidney development, embryonic blastema cells can persist and proliferate to form a pool of cells, which under either genetic or epigenetic influence can then change to become a neoplastic rest. Normally the majority of nephrogenic rests either regress or become dormant.
mesonephros - The second temporary stage of kidney development (pro-, meso-, meta-). The intermediate mesonephros develops and disappears with the exception of its duct, the mesonephric duct, which will form the male reproductive duct system. In males, the mesonephric tubules go on to form the ducts of the testis. In females, these degenerate. A few mesonephric tubules remain as efferent ductules in the male and vestigial remnants in the female.
mesonephric duct - (= Wollfian duct) An early developing urogenital duct running the length of the embryo that will differentiate and form the male reproductive duct system. In females this duct degenerates (some remnants may remain associated in broad ligament).
metanephros - The adult kidney, third stage of mammalian kidney (pro-, meso-, meta-) development within the intermediate mesoderm.
metanephric cap - In kidney development, the intermediate mesoderm which surrounds the ureteric bud and will develop into nephrons.
Multicystic Kidney - There is no functional kidney tissue present in the kidney and it is replaced by a multilocular cyst. This is non-familial and is produced by atresia of a ureter and is always unilateral.
neoplastic rest - In kidney development, a neoplastic rest can develop under either genetic or epigenetic influence from a hyperplastic rest, originating from an embryonic blastema cell. Normally the majority of nephrogenic rests either regress or become dormant.
nephrogenic rest - A kidney term used to describe the embryonic blastema cells which persist and under either genetic or epigenetic can change to become a neoplastic rest. These neoplastic rests can develop postnatally as a benign form (adenomatous rest) or a malignant Wilm's tumour form. The rests are further characterised by the time of generation leading to different anatomical kidney locations: early intralobar nephrogenic rests (within the renal lobe) and late pelilobar nephrogenic rests (periphery of the renal lobe) (More? Wilm's tumour | Urogenital Abnormalities)
nephron - (Greek, nephros = kidney) The functional unit of the kidney.
nephros - (Greek, nephros = kidney) Term used to describe features associated with the kidney. (pronephros, mesonephros, metanephros, nephric, nephron, nephroblastoma)
pronephros - (Greek, pro = before) The first temporary stage of kidney development (pro-, meso-, meta-). This forms the kidney of primitive fish and lower vertebrates. Kidney development occurs within the intermediate mesoderm interacting with endoderm. In humans, this very rudimentary kidney forms very early at the level of the neck. It is rapidly replaced by the mesonephros, intermediate stage kidney, differentiating in mesoderm beneath.
proteinuria - The abnormal presence of protein in the urine and an indicator of diesease including diabetic kidney disease (DKD, diabetic nephropathy).
renal - (Latin, renes = kidney) Term used in relation to the kidney and associated structures (renal pelvis, renal artery)
ureter - The two ureters are hollow tubes that link and carries urine from kidney to the bladder. The tubes have a muscular wall lined with transitional epithelium.
urethra - The single muscular tube that links and carries urine from the bladder to the exterior. In humans, the urethral length differs between the sexes (male longer, female shorter).
urinary - Term used to describe all components of the kidney system including the bladder, ureters and urethra.
urine - Term used to describe the liquid waste produced by the kidney, stored in the bladder and excreted from teh body through the urethra.
urorectal septum - (URS) The structure which develops to separate the cloaca (common urogenital sinus) into an anterior urinary part and a posterior rectal part.
Wilms' tumour - A form of kidney/renal cancer (nephroblastoma) named after Dr Max Wilms who first described the tumor. This childhood kidney cancer is caused by the inactivation of a tumour suppressor gene (BRCA2) or Wilms tumor-1 gene (Wt1) and is one of the most common solid tumors of childhood, occurring in 1 in 10,000 children and accounting for 8% of childhood cancers. Wt1 also required at early stages of gonadal development. (More? Kidney Abnormal Development | OMIM - Wilm's tumour | Dr Max Wilms)
Wilms' tumor 1-associating protein - (WTAP) protein expressed in extraembryonic tissues and required for the formation of embryonic mesoderm and endoderm.
Wolffian duct - (= mesonephric duct, preferred terminology), runs from the mesonephros to cloaca, differentiates to form the male vas deferens and in the female regresses. Named after Caspar Friedrich Wolff (1733-1794), a German scientist and early embryology researcher and is said to have established the doctrine of germ layers. (More? Caspar Friedrich Wolff)
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These notes cover development of the kidney functional unit, the nephron.
The kidney goes through several stages of development before establishing the mature kidney.
The functional unit of the kidney, the nephron, develops through a classical epithelial/mesenchyme type of interaction.
The gonads have quite different origins and developmental features, but are closely physically associated. A new more specific section of notes is being developed covering male and female gonad and genital development.
Please email Dr Mark Hill if you wish to make a comment about this current project.
