branching morphogenesis

Question 1

what is a metanephros?

Answer 1

definitive kidney

Question 2

what is GDNF

Answer 2

neurotrophic factor

promotes cell proliferation, migration + outgrowth

Question 3

what occurs during the branching morphogenesis of the ureteric bud?

Answer 3

1. GDNF secreted from metanephric mesenchyme and binds to Ret receptor on ureteric bud
2. signal transduction pathway activated
   TFs upregulates which act intrinsically
3. proliferation and outgrowth of tip cells occurs.
   - cells in middle of tip cells receive more GDNF signal - arrests proliferation = flatterning of bud
   - lateral tip cells receive intermediate levels of GDNF - continue to proliferation
   results in a cleft and 2 tips
4. lateral tip cells are still surrounded by mesenchyme so process repeats
   branch structures are built up

Question 4

how does a functional nephron form from metanephric mesenchyme?

Answer 4

1. ureteric bud signals locally to metanephric mesenchyme to induce condensation around the bud and an epithelial-to-mesenchymal transition
2. renal epithelium forms then renal vesicle forms
3. renal vesicle proliferates to form s shaped body
4. s shaped body becomes larger over time
5. s shaped body becomes polarised
   - at distal end, fuses with ureteric bud via selective apoptosis
   - at proximal end provides local signals for angiogenesis so endothelial capillaries are attracted
6. functional nephron formed
7. ureteric bud undergoes repeated branching morphogenesis and forms 10^6 renal vesicle inducing buds in each kidney

Question 5

what are the signalling events that occur during the branching morphogenesis of the respiratory diverticulum?

Answer 5

1. FGF10 secreted from mesenchyme binds to FGF receptor on endothelial epithelial cells of nearby respiratory diverticulum
2. respiratory diverticulum responds by proliferation and outgrowth towards the FGF10 source
3. cells at leading tip of respiratory diverticulum receive highest concentrations of FGF10 signals –> cell upregulates BMP4, Shh and then Sprouty2
   - BMP4 autonomously inhibits cell proliferation —> flattening of bud
   - Shh diffuses to mesenchyme and inhibits FGF10 in mesenchyme nearest to the tip –> splits FGF10 expression and promotes branching
   - then, sprouty2 inhibits FGF10 to restrict branching to tip of branch

Question 6

what does the endoderm of the lung give rise to?

Answer 6

epithelial lining of trachea, larynx, pharynx + alveoli

Question 7

what does the mesoderm of the lung give rise to?

Answer 7

cartilage, muscle + connective tissue