L16 - Branching Morphogenesis Flashcards
What is branching morphogenesis essential to
The function of tissues which require a high surface area for exchange
Give examples of where branching morphgenesis occurs
Lung Ureteric bud Salivary gland Prostate Mammary gland Pancreas
Branching morphogenesis is essentially to process by which _____________ are created
Tree-like // branched structures
What are the repeating units of the kindey
Nephron
Collecting duct
Formation of the kidney arises through
Reciprocal inductive interactions between the ureteric bud and the metanephric mesenchyme
What is recirpocal induction
Cell 1 signals causing cell 2 to change
Cell 2 then signals causing a change in cell 1
what is the ureteric bud
Outpocketing of intermediate mesoderm
What is the metanephric mesenchyme
Mesenchyme which is adjacent to the uretric bud
Describe the recpeirocal inductive eventss with the ureteric bud and the metanephric mesenchyme
Either side of the midline - parallel lines of intermeidate mesoderm
At very posterior bud like stuctures form - ureteric bud
ureteric bud pokes into mesodermal cells - metanephric mesenchyme
Interaction repeats throughout development
What are the (4) key steps in branching morphogenesis of the ureteric bud
Signals from the metanephric mesenchyme cause proliferation and outgrowth of bud tip cells
Leading edge tip cell arrests its proliferation resulting in the flattening of the bud
Lateral tip cells contunue proliferating –> formation of a cleft and two tips
Lateral tip cell still surrounded by mesencehyme and the process repeats
What is the signal from the metanephric mesenchyme - what is its receptor
GDNF
Ret
What type of receptor is Ret
RTK
Why do leading edge tip cells arrest their proliferation
See very high levels of GDNF and this has the effect of inhibiting proliferation
Why are lateral tip cells still able to proliferate>?
Since they only see intermediate levels of GDNF signalling
This has the effect of causing cell proliferation
GDNF from the
Acting on RET receptors of the
Metanephric mesenchyme
Ureteric bud
What is the effect of signals from the metanephric mesenchyme (what do they cause in order to get reshaping)
Activate signalling pathways
Changes in gene expression
Cellular response
What cellular responses are involved with the bifuraction of the ureteric bud
Local proliferation Oriented division Cell migration Cell adhesion Shape ECM remodelling
Describe what is meant by bifurcation of the ureteric bud being an itterative process
It is a repeated process which will form many branches
The many branches formed from the ureteric bud will form
The mutliple collecting ducts of the kidney
What happens at the same time as the uteric bud is bifucating
The uteric bud signals to the local parts of metanephric mesechyme inducing them to form definitive nephric tubules
Describe what type of change the uretric bud causes to the metanephric mesenchyme
Causes it to undergo a mesenchymal to epithelial transition
When the metanephric mesenchyme undergoes a M –> E transition what is formed - what is the next strucuture formed from this process
Renal epithliumm and then the renal vesicles
Describe the stages of renal vesicle proliferation to form a nephron
Proliferation forms an S shaped body
One end of S shaped body fuses with the collecting duct
Other end of the S shaped body attracts blood vessels and leads to the formation of the glomerulus
What happens to the DISTAl end of the S shaped body
Fuses with the uretric bud - collecting duct
The ureteric bud undergoes ________
Repeated branching morphogenesis
How many renal vesicle inducing buds in each kidney
10 million
Describe a method of studying renal development in real time
Clone promoter of a gene being expressed in the ureteric bud
Express GFP under that promoter
GFP expression can be seen in cells of the ureteric bud
Branching in the lung controlled by
FGF10 and sprout-2
Describe where our understanding of lung development came from -
Drosophila
Tracheal development in the dropsohila - molecular mechanisms used for the development of breathing apparatus are highly conserved ``
what two tissues in the lung derived from
Endoderm and mesoderm
Endoderm forms what lung strucutures
Epithelilal lining of the trachea
Larynx
Bronchi
Alveoli
Mesoderm forms what lung strucutres
Cartilage
Muscle
Connective tissue
Trachea, bronchi, bronchioles and alveoli all arise from the
Respiratory diverticulum
What does the respiratory diverticulum grow out off
Trachea
Outgrowth of the respiratory diverticulum is dependent on
Signals from the adjacent mesoderm/mesnechyme
What surrounds each lung bud
Sac of mesoderm
What is the medial edge of the sac of mesoderm lining the lungs
Visceral pleura
What is the outer edge of the sac of mesoderm lining the lungs
Parietal pleura
Endothelilal cells expres ____________ that means they are able to respond to ________ from the surrounding mesenchyme
FGFR
FGF10 - from the surrounding mesenchyme
Describe the effect of exposing the tip cells to high concentrations of FGF10
Induces the expression of secondary genes in the tip
What seocndary genes are expressed in the tip in response to FGF10
BMP4
Shh
Sprouty
Expression of the seocnary genes turns the tips into
Signalling ccentres
Describe where BMP4 expression is highest
What is the effect that this has here
In the leading edge tip cells
Inhibits epitehial cell proliferation - causes flattening
What is the effect of Shh in the lung tip
Diffuses to the mesenchyme and inhibits expression of FGF10 nearing to the tip
This splits FGF10 expression nearest the tip
What is the effect of Sprout-2
Limits the action of FGF10
Means that branching is restricted to the very tip
Describe the neative feedback loop of FGF10 and sprouty
Over a slightly longer timefram FGF10 induces expression of sprouty
Sprouty inhibts FGF signalling
What are the three periods in the development of lung tissue
Canalicular period
Terminal sac period
Alveolar period
What happens in the terminal sac period
Formation of type 1 sqamous cells (pneumocytes_
What happens in the alveolar sac period
production of type 2 squamous cells involved in the production of surfactant
How is the extensive capillary network required for gas exchange created
Alveoli generated which attracts endothelial blood cells
