Renal System Development
|Embryology - 23 Nov 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Objectives
- 4 Textbook References
- 5 Renal Movies
- 6 Background
- 7 Kidney Anatomy
- 8 Intermediate Mesoderm
- 9 Mesonephric Duct
- 10 Nephros Development
- 11 Nephron
- 12 Embryonic Kidney
- 13 Fetal Kidney
- 14 Endocrine Kidney
- 15 Cloaca
- 16 Kidney Ascent
- 17 Renal Arteries
- 18 Abnormalities
- 19 Molecular
- 20 References
- 21 Additional Images
- 22 Terms
- 23 External Links
- 24 Glossary Links
The paired adult kidneys consist of a functional unit called the "nephron", that filters blood, excretes waste, reabsorbs water (and other compounds) and has endocrine functions. Each adult human kidney typically contains about 750,000 nephrons, though the total number can vary significantly from as few as 250,000 to as many as 2,000,000.
In the embryo, nephron development, nephrogenesis, occurs through several stages involving classical epithelial/mesenchyme type of interactions. Nephrogenesis continues into the late fetal period (GA week 34–35) and while the fetal kidney does produce urine, not until after birth does the glomerular filtration rate (GFR) increases rapidly due to a postnatal drop in kidney vascular resistance and an increase in renal blood flow.
The urinary system is developmentally and anatomically associated with genital development, often described as the "urogenital system". (More? Genital System Development)
|Renal Links: Introduction | Lecture - Renal | Lecture Movie | Urinary Bladder | Stage 13 | Stage 22 | Fetal | Renal Movies | Stage 22 Movie | Histology | Abnormalities | Molecular | Category:Renal|
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Karthik Gadabanahalli, Venkatraman Bhat Thoracic Origin of Single Right Renal Artery: Some Interesting Facets. Int. J. Angiol.: 2017, 26(4);264-266 PubMed 29142495
Yousuf M Al Suleimani, Aly M Abdelrahman, Turan Karaca, Priyadarsini Manoj, Mohammed Ashique, Abderrahim Nemmar, Badreldin H Ali The effect of the dipeptidyl peptidase-4 inhibitor sitagliptin on gentamicin nephrotoxicity in mice. Biomed. Pharmacother.: 2017, 97;1102-1108 PubMed 29136947
Ahmed M Kabel, Aliaa Atef, Remon S Estfanous Ameliorative potential of sitagliptin and/or resveratrol on experimentally-induced clear cell renal cell carcinoma. Biomed. Pharmacother.: 2017, 97;667-674 PubMed 29101811
Lara De Tomasi, Pierre David, Camille Humbert, Flora Silbermann, Christelle Arrondel, Frédéric Tores, Stéphane Fouquet, Audrey Desgrange, Olivier Niel, Christine Bole-Feysot, Patrick Nitschké, Joëlle Roume, Marie-Pierre Cordier, Christine Pietrement, Bertrand Isidor, Philippe Khau Van Kien, Marie Gonzales, Marie-Hélène Saint-Frison, Jelena Martinovic, Robert Novo, Juliette Piard, Christelle Cabrol, Ishwar C Verma, Ratna Puri, Hubert Journel, Jacqueline Aziza, Laurent Gavard, Marie-Hélène Said-Menthon, Laurence Heidet, Sophie Saunier, Cécile Jeanpierre Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice. Am. J. Hum. Genet.: 2017, 101(5);803-814 PubMed 29100091
Simone Sanna-Cherchi, Kamal Khan, Rik Westland, Priya Krithivasan, Lorraine Fievet, Hila Milo Rasouly, Iuliana Ionita-Laza, Valentina P Capone, David A Fasel, Krzysztof Kiryluk, Sitharthan Kamalakaran, Monica Bodria, Edgar A Otto, Matthew G Sampson, Christopher E Gillies, Virginia Vega-Warner, Katarina Vukojevic, Igor Pediaditakis, Gabriel S Makar, Adele Mitrotti, Miguel Verbitsky, Jeremiah Martino, Qingxue Liu, Young-Ji Na, Vinicio Goj, Gianluigi Ardissino, Maddalena Gigante, Loreto Gesualdo, Magdalena Janezcko, Marcin Zaniew, Cathy Lee Mendelsohn, Shirlee Shril, Friedhelm Hildebrandt, Joanna A E van Wijk, Adela Arapovic, Marijan Saraga, Landino Allegri, Claudia Izzi, Francesco Scolari, Velibor Tasic, Gian Marco Ghiggeri, Anna Latos-Bielenska, Anna-Materna Kiryluk, Shrikant Mane, David B Goldstein, Richard P Lifton, Nicholas Katsanis, Erica E Davis, Ali G Gharavi Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations. Am. J. Hum. Genet.: 2017, 101(5);789-802 PubMed 29100090
- Understand the 3 main stages of kidney development.
- Understand development of the nephron and renal papilla.
- Brief understanding of the mechanisms of nephron development.
- Understand the development of the cloaca, ureter and bladder.
- Brief understanding of abnormalities of the urinary system.
- The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter 13 p303-346
- Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 10 p261-306
- Mesoderm then intermediate mesoderm
- Vascular Development
- Cloacal development
- Endocrine - covered in future lecture/lab
- Nephron - Functional unit of kidney
- Humans up to 1 million
- Filtration of waste from blood
- Blood pressure regulation
The key structure of the adult nephron is the glomerulus (renal corpuscle), which represents the initial vascular/renal interface.
- Bladder - Urine storage
- Endoderm allantois
- Intermediate mesoderm - Lies between somites and lateral plate
Week 3 - Stage 7 dorsal view
Cross-section showing mesoderm regions
Later in development, both the mesonephric duct and the cloaca both continue to differentiate and undergo extensive remodelling (and renaming)
- arise near the cloacal connection of the mesonephric duct
- branch from the mesonephric duct laterally into the intermediate mesoderm
- induce the surrounding mesoderm to differentiate - metanephric blastema
- this mesoderm will in turn signal back to differentiate the ureteric bud
Epithelial - mesenchymal interaction
Ureteric Bud forms - ureter, pelvis, calyces, collecting ducts
- forms glomeruli, capsule, nephron tubules
- this development continues through fetal period
Three pairs appearing in sequence within intermediate mesoderm during development.
- week 4 few cells in cervical region fish
- Human E18, Mouse E7.5pronephric duct forms first with associated nephrogenic mesenchyme
- grows rostro caudally cervical -> cloaca
- E22 nephrogenic mesenchyme differentiates to form pronephroi not functional in mammals degenerates rapidly
| Human E24, Mouse E9.5 caudal to pronephros
Week 5 - Stage 13 mesonephros
Week 8 - Stage 22 mesonephros
- Human E35-37, Mouse E11 epithelia bud at end of mesonephric duct ureteric bud and associated metanephric mesenchyme
- induced by metanephric mesenchyme to differentiate
- forms collecting tubules, renal pelvis, ureter
- metanephric mesenchyme induced by ureteric to differentiate forms nephron
|In humans, nephrogenesis only occurs before birth, though nephron maturation continues postnatally. Mean glomerular number shown to level at 36 weeks, increasing from about 15,000 at 15 weeks to 740,000 at 40 weeks.||
Adult nephron structure
Nephron development has four identifiable developmental stages:
- Vesicle (V) stage (13-19 weeks, second trimester)
- S-shaped body (S) stage ( 20-24 weeks, second trimester)
- Capillary loop (C) stage (25-29 weeks, third trimester)
- Maturation (M) stage (infants aged 1-6 months, neonatal and postnatal)
- cyst invaginates twice to form a comma
- then a S-shaped body one invagination site later becomes the glomerular cleft
- At about this time blood vessel progenitors invade cleft to begin construction of vascular component of glomerulus
- Tubule maturation specialised transporting segments of nephron differentiate complex of convoluted tubules is created
Renal Development Interactions
- 12 - 29 somite embryo mesonephros tubules begin at the level of somite 8 and are distinct as far caudally as somite 20, whence they extend as a continuous nephrogenic cord to t he level of somite 24. Opposite each somite there are two or more tubules. Thus they are not metameric, any more than the mesonephric duct is metameric, or the umbilical vein. The number of nephric vesicles is being increased by progressive differentiation caudally from the nephrogenic cord. The mesonephric duct at first ends blindly immediately short of the cloaca, but soon becomes attached to the cloaca (i.e., to the terminal part of the hindgut) and acquires a lumen.
- 13 - Mesonephros glomeruli begin to develop, and nephric tubules become S-shaped. A ureteric bud may possibly be present in some specimens fig. 4), although further confirmation is needed. The mesonephric duct, which becomes separated from the surface ectoderm except in its caudal portion, is fused to the cloaca, into which it may open. A urorectal cleavage line is apparent.
- 14 - In embryos of this stage the mesonephros is well along in its organogenesis. The steps in this process are made easier to follow by the fact that the development occurs progressively in a rostrocaudal direction. Here again is an organ in which the epithelial elements constitute its primary tissue and seem largely to determine its form. The non-epithelial mesonephric elements, though necessary complements for epithelial-mesenchymal interaction, give the appearance of being subsidiary. It has already been seen that the coelomic surface cells possess various inherent potentialities. The surface of the coelom can be mapped in definite areas in accordance with the distribution of these various kinds of surface cells. Running along each side of the median plane is a narrow strip of coelom where, by the proliferation and delamination of its surface cells, there is produced a longitudinal series of epithelial tubules that constitute the units of the mesonephros. This follows the manner in which nephric elements were formed in previous stages, and it is now about to be repeated, with certain modifications, in the development of the metanephros, which is still in the primordial state of a budding ureter with its nephrogenic capsule (fig. 14-6). One can go a step further in regard to the inherent constitution of these coelomic epithelial tubules. Not only do they become tubules, but from the beginning they show regional differentiation. The proximal end promptly blends with and opens into the mesonephric duct, and this part of the tubule persists as a collecting duct. The distal free end at the same time begins its expansion into a highly specialized part of the tubule, namely the mesonephric corpuscle. The intervening central segment of the tubule becomes the convoluted secretory portion. Embryos in this stage are especially favorable for the study of the process of formation of the mesonephric corpuscle. The proliferation of the tubular epithelium at the free end results in its maximum expansion. This occurs in such a way as to produce an indented flattened vesicle, known as a glomerular capsule. As seen in section, it has an arched floor-plate several cells thick and a thin, single-layered roof membrane. The two are continuous with each other but are very different in their potentialities. The roof membrane becomes attenuated as an impermeable membrane. The floor plate continues active proliferation and many of its cells were believed by Streeter to delaminate and apparently become angioblasts, participating in the formation of the vascular glomerulus and its supporting tissues. It is now maintained, however, that the glomerular capillaries (in the metanephros) come from adjacent vessels and never develop in situ from epithelial cells (Potter, 1965). Further details of renal development have been provided by several authors (e.g., Potter, 1972). The residual cells facing the capsular lumen in the mesonephros at stage 14 are reduced in the more advanced phases to a single layer, covering and conforming everywhere to the tabulations of the underlying capillary tufts. Angiogenesis around the secretory part of the tubule is not far advanced. Angiogenic strands connect with the caudal cardinal vein, and throughout the mesonephros there are isolated clumps of angioblasts, particularly around the capsules. These show the typical difference in complexity of the three parts of the tubule: (1) collecting duct, (2) secretory segment, and (3) glomerular capsule.
- 15 - The ureteric bud is longer, and its tip is expanded as the pelvis of the ureter (fig. 15-10). The primary urogenital sinus is distinguishable.
- 16 - The metanephros, which is now reniform, is still sacral in level. The ureter is elongating and, in more advanced embryos, the pelvis of the ureter divides into rostral and caudal poles. The urorectal septum, the formation of which is disputed, is well marked.
- 17 - The mesonephros shows epithelial plaques in the visceral layer of the glomerular capsule and hence can produce urine (Silverman, 1969). The pelvis of the ureter usually shows three main divisions, and calices appear. The urogenital sinus presents a pelvic part (vesico-urethral canal) and a phallic part (definitive urogenital sinus).
- 18 - Collecting tubules develop from the calices at stages 17 and 18. They are surrounded by sharply outlined condensed primordia in the process of forming secretory tubules. Renal corpuscules are not yet present. By stage 18 the mesonephric duct and the ureter open almost independently into the vesico-urethral canal: i.e., the common excretory duct is disappearing. The cloacal membrane is ready to rupture.
- 20 - The external surface of the metanephros is said to be slightly lobulated. A reconstruction of the urinary system has been published by Shikinami (fig. 5).
- 21 - Metanephros is spoon-shaped glomerular capsules are developing, but no large glomeruli are present yet.
- 22 - Metanephros has a few large glomeruli present.
- 23 - Comparison between the mesonephros and the metanephros in staged embryos is lacking. In metanephros, the kidneys have ascended from a sacral level at stages 13–15 to a lumbar level at stages 17–23. At stage 23 they are generally at the level of lumbar vertebrae 1–3..
|MRI appearance of normal fetal kidney. Sagittal T2- SSFSE of a fetal abdomen at GA 25 week. Adequate volume of the amniotic fluid and the developing lungs indicate good renal function.
Note that the urinary bladder can occupy a considerable portion of the abdomen as a normal finding.
|Fetal nephron development|
After nephron development has completed and concomitant with the development of the renal papilla in the newborn, the thin ascending limb of Henle’s loops is generated as an outgrowth from the S3 segment of the proximal tubule and from the distal tubule anlage of the nephron.
Covered also in Endocrine Development lecture
Common Urogenital Sinus
Can be described anatomically by its 4 layers from outside inward:
Note: Frequently a second renal artery (inferior renal) from abdominal aorta at a lower level, supplies lower portion of kidney
There are many different forms of renal development abnormalities associated with kidney, ureters, bladder and urethra. There are many genetic disorders associated with failure or abnormal renal development. Prenatal diagnosis of obstructive and renal agenesis/dysgenesis disorders are also important for early reproductive decisions by the parents. For example, with bilateral renal agenesis, failure of both kidneys to development, is not compatible with fetal/neonatal survival. Because of their close developmental association, often described as the urogenital system, there can be an associated genital abnormalities.
Urorectal Septum Malformation
Ureter and Urethra
Polycystic Kidney Disease
Prune Belly Syndrome
The Bosniak classification system (Category I - IV) was designed to separate identified cystic renal masses by analysis of computed tomography (CT) features into surgical and nonsurgical categories. Named after Morton Bosniak, Yale University School of Medicine, the developer of this classification system.
Peter Hohenstein, Kathy Pritchard-Jones, Jocelyn Charlton The yin and yang of kidney development and Wilms' tumors. Genes Dev.: 2015, 29(5);467-82 PubMed 25737276
Melissa Little, Kylie Georgas, David Pennisi, Lorine Wilkinson Kidney development: two tales of tubulogenesis. Curr. Top. Dev. Biol.: 2010, 90;193-229 PubMed 20691850
Gregory R Dressler Advances in early kidney specification, development and patterning. Development: 2009, 136(23);3863-74 PubMed 19906853
Odyssé Michos Kidney development: from ureteric bud formation to branching morphogenesis. Curr. Opin. Genet. Dev.: 2009, 19(5);484-90 PubMed 19828308
Kimberly J Reidy, Norman D Rosenblum Cell and molecular biology of kidney development. Semin. Nephrol.: 2009, 29(4);321-37 PubMed 19615554
Susan E Quaggin, Jordan A Kreidberg Development of the renal glomerulus: good neighbors and good fences. Development: 2008, 135(4);609-20 PubMed 18184729
Andrea Brenner-Anantharam, Cristina Cebrian, Richard Guillaume, Romulo Hurtado, Tung-Tien Sun, Doris Herzlinger Tailbud-derived mesenchyme promotes urinary tract segmentation via BMP4 signaling. Development: 2007, 134(10);1967-75 PubMed 17442697
Forefronts Symposium on Nephrogenetics: from development to physiology March 8-11, 2007 Danvers, MA A meeting to synthesize an integrated view of the normal development and function of the kidney from the genetic standpoint.
Frank Costantini Renal branching morphogenesis: concepts, questions, and recent advances. Differentiation: 2006, 74(7);402-21 PubMed 16916378
Mor Grinstein, Ronit Yelin, Doris Herzlinger, Thomas M Schultheiss Generation of the podocyte and tubular components of an amniote kidney: timing of specification and a role for Wnt signaling. Development: 2013, 140(22);4565-73 PubMed 24154527
Malin M Rhodin, Brian J Anderson, A Michael Peters, Malcolm G Coulthard, Barry Wilkins, Michael Cole, Etienne Chatelut, Anders Grubb, Gareth J Veal, Michael J Keir, Nick H G Holford Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr. Nephrol.: 2009, 24(1);67-76 PubMed 18846389
Open table below to see list of renal terms.
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Cite this page: Hill, M.A. 2017 Embryology Renal System Development. Retrieved November 23, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Renal_System_Development