Lung development
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The lungs are derived from 2 tissues?
Endoderm and mesoderm
Where does the respiratory diverticulum come from?
A ventral outgrowth of the foregut Forms the trachea
What does the tip of the respiratory diverticulum undergo?
Branching morphogenesis
What forms around each lung bud?
A sac of mesoderm- medial edge= visceral pleura outer edge= parietal pleura
What does nearby mesenchyme express? And what does it cause?
FGF10- induces expression of bud formation and bud extension of endothelial epithelial cells
What does high exposure to FGF10 cause?
The epithelial tip cells start to express secondary genes- Shh, BMP4, Sprouty2
What does high expression of BMP4 cause?
Inhibition of epithelial cell proliferation- limiting branch extension
What does Shh expression by the tip cells cause?
Inhibition of FGF10 expression in the mesenchyme nearest the tip- splits expression of FGF10
What does Sprouty limit?
The action of FGF10 so that branching is restricted to the tip of the branch
Which cells are produced in the terminal sac period?
Type 1 squamous cells
Which cells are produced in the alveolar period?
Type 2 cells- surfactant producing
What continues after birth?
Respiratory bronchioles and alveoli growth
How do we study such complex cell behaviours in 3D?
• In vivo approaches- investigate using conditional KOs • Investigate in a 3D organ culture?- dissected embryonic mouse lung- (importance of lung mesenchyme) • Look at tissues- using sophisticated microscopy
What can happen if a cell loses apico-basal polarity?
No longer recognises the need to be a epithelial cell and can leave the epithelium- cancer