L9- Organogenesis Flashcards
What are the main features of kidney development?
- Induction
- Mesenchyme to epithelial changes (reciprocal signalling)
- Branching morphogenesis
- Formation of the glomerulus
- Nephron formation
What is the Wolffian duct?
- Forms from the intermediate mesoderm
* Runs down the length of the body and forms the uteric bud which branches to form nehphric buds and kidney structures
How is the filtration unit organised in zebrafish?
Single glomerulus filters blood from the dorsal aorta and the filtrate is removed by a pair of pronephric tubules
How is the filtration unit organised in zenopus?
Glomerulus discharges filtrate from blood into body cavity. Filtrate is driven into pronephric ducts by cilia.
How is the filtration unit organised in birds?
Metanephric kidney which does not degenerate in adulthood
How is kidney formation induced?
The nephrogenic mesenchyme induces formation of the ureteric bud from the Wolffian duct.
What influences the position of the kidney formation?
The mesenchyme adjacent to where the ureteric bud will form expresses 3 HOX transcription factors (aII, cII, dII)
If these are knocked out the metanephric mesenchyme cannot differentiate and does not express GDNF
What does GDNF do?
- GDNF signals to the Wolffian duct through Ret transmembrane receptor and induces outgrowth of the bud.
- Mice lacking GDNF or Ret receptor lack ureteric buds, and therefore kidneys
What is reciprocal signalling?
The ureteric buds signal back to metanephric mesenchyme cells to keep them alive
How does reciprocal signalling work?
- Ureteric bud secretes BMP7 and FGF2 signalling proteins
- Both prevent mesenchyme cells from dying
- By maintaining expression of WT1 transcription factor (mesenchyme dies without this)
- FGF2 also promotes further mesenchyme condensation
What prevents ureteric buds forming elsewhere along the Wolffian duct?
- Mesenchyme secretes BMP4 signalling protein
- This prevents formation of buds other than where GDNF is secreted
- GDNF overrides the BMP4 signal
- So BMP4 ensures kidney is only formed in the correct location
What happens in mesenchymal-epithelial changes?
The ureteric bud secretes Wnt9b and LIF signalling proteins to introduce mesenchymal cells to become tubules
What happens in branching morphogenesis?
Development of multiple nephrons from the ureteric bud by branching and condensation of the mesenchyme
• Highly regulated
What signalling proteins are involved in morphogenesis?
- GDNF from mesenchyme induce ureteric bud to branch TGFβ1 stabilises branches
- Wnt11 from bud tips maintains GDNF (reciprocal)
- Condensed mesenchyme secretes Wnt4 protein which signals to the cells that make it to begin nephron formation (autocrine)
What is the difference between mesenchyme and epithelium?
Mesenchyme is a loose arrangement of cells whereas epithelium (especially of the nephron) is more regulated
