Renal System Development
Embryology - 27 Apr 2024 Expand to Translate |
---|
Google Translate - select your language from the list shown below (this will open a new external page) |
العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt These external translations are automated and may not be accurate. (More? About Translations) |
Introduction
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.[1][2]
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)
Some Recent Findings
|
More recent papers |
---|
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Renal Embryology <pubmed limit=5>Renal Embryology</pubmed> |
Objectives
- 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.
Textbook References
- 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
Renal Movies
|
|
|
| ||||||||||||
|
|
|
Background
- Mesoderm then intermediate mesoderm
- Vascular Development
- Gastrointestional
- Cloacal development
- Endocrine - covered in future lecture/lab
Kidney Anatomy
- Nephron - Functional unit of kidney
- Humans up to 1 million
- Filtration of waste from blood
- Endocrine
- Blood pressure regulation
The key structure of the adult nephron is the glomerulus (renal corpuscle), which represents the initial vascular/renal interface.
Related Images: Nephron histology overview | glomerulus structure | vascular and renal poles
Ureter
- Bladder - Urine storage
- Endoderm allantois
Mesoderm
- Intermediate mesoderm - Lies between somites and lateral plate
Intermediate Mesoderm
- development occurs laterally symmetrical (left right)
- intermediate mesoderm lying beside the dorsal aorta
- initially form mesonephric tubules (epithelial)
- these tubules connect to a common duct, mesonephric duct
- the mesonephric duct then extends within the mesoderm, rostro-caudally
- eventually making contact with the cloaca
Mesonephric Duct
Later in development, both the mesonephric duct and the cloaca both continue to differentiate and undergo extensive remodelling (and renaming)
Ureteric Bud
- 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
Metanephric Blastema
- forms glomeruli, capsule, nephron tubules
- this development continues through fetal period
Nephros Development
Three pairs appearing in sequence within intermediate mesoderm during development.
- pronephros
- mesonephros
- metanephros
Pronephros
- 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
Mesonephros
- Human E24, Mouse E9.5 caudal to pronephros
- forms by induction from pronephros
- pronephric duct now becomes mesonephric duct (also called Wolffian Duct)
Metanephros
- Human E35-37, Mouse E11 epithelia bud at end of mesonephric duct ureteric bud and associated metanephric mesenchyme
Ureteric Bud
- induced by metanephric mesenchyme to differentiate
- forms collecting tubules, renal pelvis, ureter
- metanephric mesenchyme induced by ureteric to differentiate forms nephron
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.
Nephron development has four identifiable developmental stages:
|
|
Nephron Development
- disorganised mesenchymal cells become a highly organised epithelial tubule
- Condensation - groups of about 100 cells condense tightly together to form a distinct mass
- Epithelialisation - condensed cells lose their mesenchymal character and gain epithelial
- At end of this period formed a small epithelial cyst complete with a basement membrane, cell-cell junctions and a defined cellular apico-basal polarity.
Early Morphogenesis
- 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[8] |
Fetal Kidney
MRI appearance of normal fetal kidney.[9] 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.
|
Endocrine Kidney
Covered also in Endocrine Development lecture
- Renin - Increase Angiotensin-aldosterone system
- Prostaglandins - decrease Na+ reabsorption
- Erythropoietin - Increase Erythrocyte (rbc) production
- 1,25 (OH)2 vitamin D - Calcium homeostasis
- Prekallikreins - (plasma protein inactive precursor of kallikrein) Increase kinin production (altered vascular permeability)
Cloaca
|
|
Common Urogenital Sinus
- superior end continuous with allantois
- common urogenital sinus and mesonephric duct fuse (connect)
- differentiates to form the bladder
- inferior end forms urethra
- this will be different in male and female development
Urinary Bladder
|
Dorsal view of developing bladder
|
Bladder Structure
Can be described anatomically by its 4 layers from outside inward:
- Serous - the superior or abdominal surfaces and the lateral" surfaces of the bladder are covered by visceral peritoneum, the serous membrane (serosa) of the abdominal cavity, consisting of mesthelium and elastic fibrous connective tissue.
- Muscular - the detrusor muscle is the muscle of the urinary bladder wall.
- Submucosa - connects the muscular layer with the mucous layer.
- Mucosa - (mucus layer) a transitional epithelium layer formed into folds (rugae).
Detrusor Muscle
- The adult detrusor muscle consists of three layers of smooth (involuntary) muscle fibres.
- external layer - fibres arranged longitudinally
- middle layer - fibres arranged circularly
- internal layer - fibres arranged longitudinally
Ureter Development
- The adult ureter is a thick-walled muscular tube, 25 - 30 cm in length, running from the kidney to the urinary bladder.
- Anatomically can be described in two parts the abdominal part (pars abdominalis) and pelvic part (pars pelvina).
- The ureter is composed of three layers: outer fibrous layer (tunica adventitia), muscular layer (tunica muscularis) and mucous layer (tunica mucosa).
- The muscular layer can also be subdivided into 3 fibre layers: an external longitudinal, a middle circular, and an internal longitudinal.
Trigone Development
Trigone |
Page | Play |
Kidney Ascent
|
|
Renal Arteries
- Arise with ascent and inferior branches lost
- Sequential, 25% population have 2 or more renal arteries
- branch of abdominal aorta, divides into 4-5 branches
- each gives off small branches to suprarenal glands, ureter, surrounding cellular tissue and muscles
Note: Frequently a second renal artery (inferior renal) from abdominal aorta at a lower level, supplies lower portion of kidney
Abnormalities
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.
More detailed information is available on the links below.
- Links: Renal Abnormalities | Genital Abnormalities
Horseshoe Kidney
- fusion of the lower poles of the kidney.
- During migration from the sacral region the two metanephric blastemas can come into contact, mainly at the lower pole.
- The ureters pass in front of the zone of fusion of the kidneys.
- The kidneys and ureters usually function adequately but there is an increased incidence of upper urinary tract obstruction or infection.
- Some horseshoe variations have been described as having associated ureter abnormalities including duplications.
Urorectal Septum Malformation
- thought to be a deficiency in caudal mesoderm which in turn leads to the malformation of the urorectal septum and other structures in the pelvic region.
- Recent research has also identified the potential presence of a persistent urachus prior to septation of the cloaca (common urogenital sinus).
Bladder
- absent or small bladder - associated with renal agenesis.
Bladder Exstrophy
- developmental abnormality associated with bladder development.
- origins appear to occur not just by abnormal bladder development, but by a congenital malformation of the ventral wall of abdomen (between umbilicus and pubic symphysis).
- There may also be other anomolies associated with failure of closure of abdominal wall and bladder (epispadias, pubic bone anomolies).
Ureter and Urethra
- Ureter - Duplex Ureter
- Urethra- Urethral Obstruction and Hypospadias
Polycystic Kidney Disease
- diffuse cystic malformation of both kidneys
- cystic malformations of liver and lung often associated, Often familial disposition
- Two types
- Infantile (inconsistent with prolonged survival)
- Adult (less severe and allows survival)
- Autosomal dominant PKD disease - recently identified at mutations in 2 different human genes encoding membrane proteins (possibly channels)
Wilms' Tumor
- (nephroblastoma) Named after Max Wilms, a German doctor who wrote first medical articles 1899
- most common type of kidney cancer children
- WT1 gene - encodes a zinc finger protein
- Both constitutional and somatic mutations disrupting the DNA-binding domain of WT1 result in a potentially dominant-negative phenotype
- some blastema cells (mass of undifferentiated cells) persist to form a ‘nephrogenic rest’
- Most rests become dormant or regress but others proliferate to form hyperplastic rests
- any type of rest can then undergo a genetic or epigenetic change to become a neoplastic rest
- can proliferate further to produce a benign lesion (adenomatous rest) or a malignant Wilms’ tumour
Prune Belly Syndrome
- lower urinary tract obstruction
- mainly male
- fetal urinary system ruptures leading to collapse and "prune belly" appearance.
Renal Cysts
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.[10] Named after Morton Bosniak, Yale University School of Medicine, the developer of this classification system.
Molecular
Abbreviation | Growth Factor | Renal Development | Expression Location |
---|---|---|---|
BMP4 | Bone Morphogenetic Protein 4 | prevents ectopic ureteric bud outgrowth and extra ureteric bud divisions | mesenchymal cells surrounding mesonephric duct and stromal mesenchyme surrounding steric bud stalks |
BMP7 | Bone Morphogenetic Protein 7 | survival of metanephric mesenchyme | metanephric mesenchyme |
Fgf8 | Fibroblast Growth Factor 8 | transition of the induced cap mesenchyme into RVs | cap mesenchyme |
GDNF | Glial-cell derived neurotrophic factor | induces steric bud outgrowth from mesonephric duct, interacts with Ret | metanephric mesenchyme |
VEGF | Vascular endothelial growth factor | promotes endothelial cell proliferation, differentiation | s-shaped body |
Wnt4 | Wingless-Type MMTV Integration Site Family, Member 4 | mesenchymal-to-epithelial transition | cap metanephric mesenchyme, pre-tubular aggregate, nephron progenitors |
Wnt5a | Wingless-Type MMTV Integration Site Family, Member 5a | nephrogenesis induction, ectopic bud formation | steric bud, metanephric mesenchyme |
Wnt9b | Wingless-type MMTV integration site family, Member 9B | renewal and differentiation of nephron progenitors and normal ureteric bud branching, mesenchymal-to-epithelial transition | steric bud stalk epithelial cells |
- Foxd1 - (Brain Factor-2) transcription factor that is a renal stroma specific gene.
- Links: Renal System - Molecular | OMIM Foxd1
References
- ↑ <pubmed>1546799</pubmed>
- ↑ <pubmed>17495859</pubmed>
- ↑ <pubmed>22253716</pubmed>
- ↑ <pubmed>25758227</pubmed>
- ↑ <pubmed>22253716</pubmed>
- ↑ <pubmed>21110022</pubmed>
- ↑ <pubmed>20810610</pubmed>
- ↑ <pubmed>25737276</pubmed>
- ↑ <pubmed>25685519</pubmed>| J Adv Res.
- ↑ <pubmed>16040900</pubmed>| Radiology
Textbooks
- 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
- Before We Are Born (5th ed.) Moore and Persaud Chapter14 p289-326
- Essentials of Human Embryology, Larson Chapter 10 p173-205
- Human Embryology, Fitzgerald and Fitzgerald Chapter 21-22 p134-152
Online Textbooks
Search Bookshelf intermediate mesoderm | kidney development | renal development | ureteric bud | nephron development | bladder development
- Developmental Biology by Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000 Chapter 14 Intermediate Mesoderm | Figure 14.18. General scheme of development in the vertebrate kidney | Figure 23-23. Mechanism of mesenchymal inductive effect on the ureteric bud | Figure 14.21. Ureteric bud growth is dependent on GDNF and its receptor
- Molecular Cell Biology by Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999 Reciprocal Epithelial-Mesenchymal Interactions Regulate Kidney Development | Figure 23-21. Embryonic development of the kidney
Reviews
<pubmed>25737276</pubmed> <pubmed>20691850</pubmed> <pubmed>19906853</pubmed> <pubmed>19828308</pubmed> <pubmed>19615554</pubmed> <pubmed>18184729</pubmed> <pubmed>17442697</pubmed> 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.
<pubmed>16916378</pubmed>
Articles
<pubmed></pubmed> <pubmed></pubmed> <pubmed>24154527 </pubmed> <pubmed>18846389</pubmed>
Search PubMed
Search Pubmed: Renal System Development | Renal Development | intermediate mesoderm | kidney development | renal development | ureteric bud | nephron development | bladder development
Additional Images
Terms
Open table below to see list of renal terms.
Renal Terms | ||
---|---|---|
| ||
|
External Links
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
- Australia - Network for Genes & Environment in Development Professor John F. Bertram
- GenitoUrinary Development Molecular Anatomy Project (GUDMAP) Renal Development Tutorial | Genital Development Tutorial
- Urine Metabolome database is a freely available electronic database containing detailed information about ~3100 small molecule metabolites found in human urine along with ~3900 concentration values.
System Links: Introduction | Cardiovascular | Coelomic Cavity | Endocrine | Gastrointestinal Tract | Genital | Head | Immune | Integumentary | Musculoskeletal | Neural | Neural Crest | Placenta | Renal | Respiratory | Sensory | Birth |
Glossary Links
- Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link
Cite this page: Hill, M.A. (2024, April 27) Embryology Renal System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Renal_System_Development
- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G