Branching Morphogenesis

Question 1

What is branching morphogenesis needed for and give some examples of where it occurs?

Answer 1

• Needed for high SA to V ration to maximise efficiency of gas, fluid or solute exchange

e.g. epithelial sheets/tubes in lung/salivary gland/pancreas

Question 2

What is the drosophila larval tracheal system?

Answer 2

• Organ responsible for gas exchange
• Develops by tracheal placode (specialised ectoderm) invaginating the membrane
• Leads to tracheal sac protrusions which are the branching tracheal tubes

Question 3

What drives the branching of tracheal epithelial branching of tip cells?

Answer 3

• Interaction of FGF-like protein called branchless (secreted by epidermal cells) with FGF-like tyrosine kinase receptor breathless (tracheal epithelial cells)
• Only breathless expressing ‘leader cells’ exposed to highest levels of branchless can form terminal unicellular branches
• When the leader cells experience branchless they produce filopodia develop filopodia, and they
  then become migratory. These migratory, so-called Leader cells, move towards extracellular sources of Branchless that pulling an elongating tube of cells behind them as a collective.

Question 4

What is the role of sprouty?

Answer 4

• Acts as a break on the branching process driven by FGF signalling so it can act as a negative regulator
• Defected = over branching

Question 5

How does the kidney develop?

Answer 5

• from the pax-2 expressing intermediate mesoderm in the trunk region (amniote embryos)
• a portion of this gives rise to the UTERIC BUD EPITHELIUM and METANEPHROGENIC MESENCHYME of the kidney
• Metanephrogenic mesenchyme controls the brancing

Question 6

How does the Uteric bud become branched?

Answer 6

• Anterior intermediate mesoderm = uteric bud and surrounding is the metanephrogenic mesenchyme
• mesenchyme releases FGF-like signalling (GDNF) acting on tyrosine kinase RET-receptor on the bud tip cells, promoting its outgrowth
• After a while the cells in the middle of the tip of the bud stop growing out and cells either side of the tip continue to grow
• These two ends then become independent of growth and further branching occurs driven by interaction between GDNF and RET receptor

**Diff to drosophila as there is BINDING involved whereas drosophila = chemoattractant moving towards vibe

Question 7

What is the vertebrate ortholog of sprouty (found in drosophila) in vertebrates and what does it do?

Answer 7

Called sprouty1
- limits branching morphogenesis in mouse uteric bud
- more sprouting found in a sprouty1 mutant