UNSW Embryology

 ANAT2341 - Embryology - Lecture 11

© Dr Mark Hill (2009)

Acknowledgements

Introduction

Lecture Notes under Development (notice removed when completed) This lecture is an introduction to the events during kidney development from intermediate mesoderm through to a functional kidney. If you are interested in further reading, I have also included below links to more detailed textbooks with further information and images. Please note this additional information is not necessarily examinable, but may be useful if you have not previously studied biology.

Early Fetal Kidney

(More? Carnegie Stages)

Page Links: Introduction | Lecture Slides | Lectopia Audio | Lecture Objectives | UNSW Embryology | Comments | Online Books | Internet Links | Next | Glossary | Terms |

Lecture Slides

These links are to PDF versions of the Lecture slides: 1 slide/page viewing 48 pages | 4 slide/page printing 12 pages | 6 slide/page printing 8 pages

Lectopia Audio link to the audio recording of Lecture 11 Kidney

The online text Online Books and UNSW Embryology links listed on this page worth reviewing for this lecture.

Lecture Objectives

• Understanding of mammalinan kidney development in 3 main stages
• Understanding of metanephric kidney nephron development
• Understanding of kidney blood supply development
• Understanding of ureter and bladder development
• Brief understanding of kidney functions and histology
• Brief understanding of kidney devevelopment in other species
• Brief understanding of kidney abnormalities of devevelopment

Lecture Summary

The following text is extracted and modified from lecture slides and should be used as a "trigger" to remind you of key concepts.

• Lecture Overview
  • Kidney
    
  • Location
    
  • Appearance
    
  • Development
    
  • Function
    
  • Abnormalities
  • Not Covered in Lecture - Gonads, Reproductive
• Background
  
  • Mesoderm
    
  • Intermediate
    
  • Vascular Development
    
  • Gastrointestional
    
  • Cloacal development
    
  • Endocrine - Covered in future lecture/lab
• Online References
  
  • UNSW Embryology - Kidney Development
    
    • http://embryology.med.unsw.edu.au/Notes/urogen.htm
      
    • http://embryology.med.unsw.edu.au/Movies/urogen.htm
  • NIH Bookshelf
    • Developmental Biology (Gilbert) Chapter 14 Intermediate Mesoderm
      http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=dbio.section.3498
  • Review of kidney development
    http://golgi.ana.ed.ac.uk/tutork.html
• Textbook References
  
  • Human Embryology (33d ed.) Larson - Chapter 10 p261-306
    
  • The Developing Human (6th ed.) Moore & Persaud - Chapter 13 p303-346
    
  • Before We Are Born (5th ed.) Moore and Persaud - Chapter 14 p289-326
    
  • Essentials of Human Embryology Larson Chapter 10 p173-205
    
  • Human Embryology Fitzgerald and Fitzgerald Chapter 21-22 p134-152
• Kidney Anatomy
• Kidney Function
  Nephron
  Functional unit of kidney
  Humans up to 1 x 106
  Filtration of waste from blood
  Endocrine
  Blood pressure regulation
  Ureter
• Bladder
  Urine storage
  Endoderm allantois
  Mesoderm
  Intermediate mesoderm
  Lies between somites and lateral plate
  Nephros Development
  3 pairs during development
  pronephros
  mesonephros
  metanephros
• Nephros Development
  pronephros
  week 4
  few cells in cervical region
  fish
  mesonephros
  week 4-8
  aorta -> renal tubules -> mesonephric duct -> cloaca
  amphibia
  metanephros
  mammals
• Pronephros
  Forms
  Human E18, Mouse E7.5
  pronephric duct
  forms first with associated nephrogenic mesenchyme
  grows rostrocaudally
  cervical -> cloaca
  E22 nephrogenic mesenchyme differentiates to form
  pronephroi
  not functional in mammals degenerates rapidly
  Movie: Pro-, Meso-,Metanephros
  Early Pronephros
  Pronephros
  Nephron Anatomy
• 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 duc
  uteric bud and associated metanephric mesenchyme
• Uteric Bud
  induced by metanephric mesenchyme to differentiate
  forms collecting tubules, renal pelvis, ureter
  metanephric mesenchyme
  induced by uteric to differentiate
  forms nephron
• Kidney
  Inductive interactions between 2 tissues
  blastema of metanephric mesenchyme (MM) arises from intermediate mesoderm
  ureteric bud a diverticulum off the nephric duct
  First interactions (probably long range) from MM
  signal chemotactic causes bud to sprout off duct
  under indirect control of WT1
  Second interaction (probably long range) from bud to MM
  causes it to divide and enter a stem-cell phase
  rather than undergo apoptosis
  Third from bud (likely to be a short-range interaction)
  causes groups of stem cells to aggregate, epithelialize and form nephrons
  Fourth is from the stem cells
  supplements initial interaction of bud growth leads to bud bifurcation
  these two interactions regulate formation of collecting duct system
  Other inductive interactions involved in later stages of nephrogenesis
• Ureteric Bud
• Movie: Nephron Development
• Nephrons
  Kidney Induction Interactions
• Nephron Development 1
  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
• Nephron Development 2
  Early morphogenesis
  cyst invaginates twice
  to form a comma and 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
  Molecular Kidney
  (A) ureteric bud (UB) from mesonephric or Wolffian duct (WD) and begins growing toward metanephric mesenchyme (MM)
  (B) UB elongates and comes into contact with loose MM, MM condenses (cMM)
  (C) UB branches to form collecting ducts (CD) and cMM undergoes an epithelial transformation and forms comma (CB) and S-shaped (SB) bodies
  (D) Nephron unit, includes glomerulus (G) and proximal tubule (PT), forms from CB and SB.
• Metanephros
  Collecting System
  uteric bud from mesonephric duct
  forms a succession of collecting tubules
  Secretory System
  metanephric cells from near collecting tubule
  forms nephron
  Function
  from mid-gestation
  forming urine into amniotic cavity
• Kidney Ascent
  Pro-, Meso-, Meta-
  Early development descending
  Metanephros
  Initially pelvic
  Beside aorta
  Growth and straightening of body
  Kidneys in abdomen
  Displace laterally
• Renal Arteries
  • Arise with ascent and inferior branches lost
  • Sequential, 25% population have 2 or more renal arteries
  • Renal artery
    • 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
• Blood Supply
  • posterior cardinal veins form
  • right subcardinal
  • right supracardinal
  • then paired subcardinal veins and supracardinal
• Movie: Blood Supply
• Endocrine Kidney
  See Lecture 21 - Endocrine Development
  Renin
  Increase Angiotensin-aldosterone system
  Prostaglandins
  decrease Na+ reabsorption
  Erythropoietin
  Increase Erythrocyte (rbc) production
  1,25 (OH)2 vitamin D
  Calcium homeostasis
  Prekallikreins
  Increase Kinin production
  Stage 13/14
  Human Kidney Stage 22
  Stage 22
  Kidney Stage 22
  Urinary Bladder
  Cloaca divided (week 6)
  Urorectal septum
  Posterior- rectum
  Anterior- urogenital sinus
  Continuous with allantois
  Apex of developing bladder
  Urachus (Median umbilical ligament)
• Movie: Bladder
  Bladder
• Kidney Abnormalities
  discussed in Lab class
• Unilateral renal agenesis
  0.1% have single kidney
  Bilateral renal agenesis
  1 in 6000 no kidney
  Polycystic kidney
  enlarged kidney
  Ectopia
  failure of kidney to ascend
  Horseshoe kidney
  Wilms' Tumor
• Polycystic Kidney Disease (PKD)
  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
• Horseshoe Kidney
• Wilms' Tumor
  • named after Max Wilms, a German doctor who wrote first medical articles 1899
  • also called nephroblastoma
  • 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
• Wilms’ Tumour
  • Some blastema 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

UNSW Embryology

The following links are to UNSW Embryology additional resources that provide further background information on the Lecture topics. Note that not all information found on these additional links is considered examinable and the lecture slides and laboratory classes should be used as your initial guide for course theory content. Links: Introduction Urogenital System | Abnormalities | References | Stage 13/14 Embryo | Stage 22 Embryo | Stage 22 Highpower | The search window below allows a search within the UNSW Embryology website.

Coordinator Comments

Dr Mark Hill

The kidneys are the processor, recycler and disposer when dealing with our bodily fluids. These lecture pages are being updated for the current course, so it is worth coming back again later to see if any changes have occurred. Please let me know by email of broken links or content that is not clearly covered in this supporting online material.

Online Books

Developmental Biology 6th ed. Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000.

Below are listed links that relate to this Lecture from the textbook "Developmental Biology" which is available free online. You can either click the provided links or do your own search using the search link.

Search Developmental Biology

Molecular Biology of the Cell 4th ed. Alberts, Bruce; Bray, Dennis; Lewis, Julian; Raff, Martin; Roberts, Keith; Watson, James D. New York and London: Garland Publishing; c2002.

Below are listed links that relate to this Lecture from the textbook "Molecular Biology of the Cell" which is available free online. You can either click the provided links or do your own search using the search link.

Search Molecular Biology of the Cell

Internet Links

Course Homepage | Course Calendar | Course Handout 2008 - PDF Document (8 pages, 192Kb) | Textbooks | Journals

Online References

Blue Histology - Urinary System |

NCBI Bookshelf | Acrobat Reader

Next

Lecture 12 - Genital Wed 13:00 - 14:00 Australian School Business 119 (K-E12-119)

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

Terms

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.

mesangial cell - (glomerular mesangial cell) Kidney epithelial cell type located in the nephron (functional kidney unit) surrounding glomerular capillaries (blood vessels). Mesodermal in origin, there are mesangial cells within (intraglomerular) and outside (extraglomerular) the glomerulus. Have several functions including: contractile activity (smooth muscle-like) controlling blood flow and basement membrane surface area (glomerular filtration rate), structural support, phagocytosis (remove basal lamina components and immunoglobulins). (More? Nephron Notes)

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)

podocyte - (glomerular podocyte) Kidney epithelial cell type in the nephron (functional kidney unit) located in the glomerulus. Podocytes are at the filtration barrier between capillary blood and the nephron tubular system and function to ultrafiltrate blood, and support glomerular capillary pressures. The differentiation of podocytes involves the formation of cellular foot processes and then the slit membrane. (More? Nephron Notes)

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)

References

These references are background reviews and research article readings and is not examinable.

Articles

• Steptoe PC, et al.

Some Recent Reviews

Articles

UNSW Embryology ISBN: 978 0 7334 2609 4

UNSW CRICOS Provider Code No. 00098G