Kidney Formation Flashcards
What are the three important tissues of the kidney?
1) Blood capillaries
2) Nephrons
3) Collecting ducts
What is the developmental term for the definitive kidney?
The metanephros
The definitive kidney arises as a result of reciprocal interactions between which two structures?
The uteric bud
Metanephric mesenchyme
What is the uteric bud?
A small outpocket of the intermediate mesoderm
When does the kideny start to form?
Around 28 days of gestation (humans)
The metanephric mesenchyme will form what?
The definitive nephric tubules
What does the uteric bud grow towards?
The metanephric mesenchyme
What does the uteric bud unduce in the metanephric mesenchyme?
It induces it to condense around the bud, undergoing a mesenchymal to epithelial transition
This forms the renal vesicle
What does the renal vesicle differentiate into?
The nephron
Which gene is important for the proliferation of the renal vesicle?
FGF
What happens distally between the renal vesicle and the bud?
They fuse
What happens distally at the renal vesicle?
It attracts endothelial capillaries
Nephrons arise from what population of the mesenchyme?
Pretubular aggregates
Which gene causes nephrons to arise?
Wnt9b
How many nephrons are there in each kidney?
10^6
Why is it possible to form so many nephrons from the uteric bud?
Because it undergoes branching morphogenesis
Describe the steps in branching morphogenesis in the uteric bud
1) Proliferation and growth of the tip cells
2) Arrest in proliferation of leading edge tip cell, resulting in flattening of the bud
3) Continued proliferation at the lateral tip cells results in the formation of a cleft and two new tips
What is the receptor on the bud?
A receptor tyrosine kinase called Ret
What signal comes from the mesenchyme?
GDNF
What is GDNF and what is its action?
Initially identified as a neurotrophic factor
Promotes proliferation, migration and outgrowth
How do we know about the formation of the kidney?
We can study the process in real time using transgenic animals
Eg using wide field epifluorescence where development has been confined to the uteric buds
In humans how many branches of the uteric bud have formed at:
a) six weeks
b) seven weeks
c) thirty two weeks
a) 16
b) Minor calyces have formed
c) 10^6 branches
What is the ureter a remnant of?
The initial bud
What are the major calyces a remnant of?
The first branch
Which transcription factor is expressed in nephron stem cells?
Six2
What is the role of Six2 and how is this shown?
It regulates the events that keep the nephron stem cell in a self renewing fate
If it is lost in LOF then the stem cell pool is depleted
If it is overexpressed then differentiation is prevented
What are the two structures called that form before the metanephros?
The pronephros
The mesenephros
Which mesoderm do kidneys form from?
The intermediate mesoderm
The intermediate mesoderm undergoes a mesenchymal to epithelial cell transition to form what two structures?
The nephric duct
The nephric cord
What does the nephric duct develop in to?
A lumen
Eventually it will give rise to the uteric bud
What does the nephric cord develop into?
Metanephric mesenchyme
Why is the pronehros not functional in mammals?
The nephric duct is fully contained in the embryo so it cannot excrete filtered fluids outside of the embryp
Mesenephric tubules attract their blood supply from where?
The nearby aorta
In males, some mesonephros tubules are retained as what?
The vas deferens
What is Wilm’s tumour?
A pediatric cancer in which kidney elements are incompletely differentiated, and instead proliferate to form tumours
Why do we need to understand the molecular details of kidney development?
To help cure some diseases eg polycystic kidney disease
Or to learn how we can make iPS cells turn into kidney cells
