Lung/Trachea Development Flashcards
Lungs are derived from which two tissues?
Endoderm
Mesoderm
Endoderm gives rise to which lung structures?
Trachea, larynx, bronchi, alveoli
Mesoder gives rise to which lung structures?
Cartilage, muscle and connective tissue
Buds made from branching morphogenesis form which lung structures?
Trachea -> Bronchi -> Bronchioles -> Alveoli
The trachea, bronchi etc rise from what?
The respiratory diverticulum
How is respiratory diverticulum formed?
The foregut splits in to the oesophagus and the trachea as a result of the hox code
In humans when do lung buds form?
During the forth week?
The outgrowth of the respiratory diverticulum is dependent on signals from where?
The adjacent mesoderm/mesenchyme
Which model organism was used to understand tracheal development?
Drosophila
Bud extension occurs because nearby mesenchyme expresseds which gene?
FGF
Exposure of high FGF induces the expression of which genes in the tip of the bud?
BMP4, Shh and Sprouty2
Where is BMP4 expressed at the highest level in the bud?
In the leading edge tip cells
What is the effect of the high BMP4 in the leading edge tip cell?
It autonomously inhibits epithelial cell proliferation so it limits branch extension and causes the bud to flatten
What is the effect of the Shh which is expressed by the tip cells?
It diffuses to the mesenchyme and inhibits FGF10 expression in the mesenchyme nearest the tip
This splits the expression of FGF10 promoting th enext round of branching
What is the action of sprouty2?
Sprouty2 limits the action of FGF10 so that branching is restricted to one end of the branch
Which of the genes expressed in the leading tip cell as a result of FGF is activated later?
Sprouty2
Why is sprouty activated later?
It is an inhibitor of FGF10 so it sets up a negative feedback loop to limit the time FGF can cause any action
By the end of 6 months of gestation how many generations of subdivisions have formed?
17
How many more divisions occur in postnatal life?
23
The formation of alveoli attracts what?
Endothelial blood cells which come in to close contact and provide an extensive network for gas exchange
What fraction of adult alveoli is present at birth?
A sixth
Why is a conditional knockout used?
This is where the gene is lost at the right place and the right time
It is used as otherwise the organism would die before you could look at the effect of losing a gene on a particular organ
Give an example of a conditional knockout experiment in mice mammary glands
Rac1 knockout in the mammary glands mean they do not undergo branching morphogenesis
They have a ‘baobab tree’ phenotype
What happens if a cell loses its apico-basal polarity?
It thinks it no longer needs to be in an epithelium, meaning it leaves and potentially causes cancer
List examples of other organs that use branching morphogenesis
Salivary gland, Prostate, Mammary gland, Pancreas
