Organogenesis Flashcards
What are the two building blocks of the kidney?
nephron + collecting duct
Where does the collecting duct originate from?
ureteric bud
Where do the nephrons originate from?
metanephric mesenchyme
Which part of the mesoderm does the kidney originate from?
the intermediate mesoderm
What proteins are involved in kidney development?
Lim1 (homeodomain TF)
Pax2 and Pax 8 (paired box TFs)
How are kidney tissues initially induced?
a signal from the paraxial mesoderm to the intermediate mesoderm (paracrine signal), molecular nature of this signal is currently unknown
AND a signal from lateral side of the embryo (paracrine signal), BMP2
What is BMP2 and how does it work?
it is a secreted morphogen that induces kidney tissue at a ‘medium level’ of activity
(i.e. switches on Pax2/Lim1 at medium conc)
How do the UB and MM ensure growth and development remain proportionate?
through local reciprocal inductive interactions, a two way conversation between cells
one cell (inducer) regulates behaviour of another cell (responder)
each cell is changed
What is the signal and what is the receptor involved in the branching of the ureteric tree?
signal: glial cell line-derived neurotrophic factor (GDNF), active in the MM
receptor: Ret, expressed in the nephric duct and tips of ureteric branches
What results if either the receptor or signal is removed during development of the nephric duct?
no budding or branching of the nephric duct
GNDF is both necessary and sufficient for budding/branching. True or False?
True
The ureteric bud tip swells and forms how many branches?
2 (occasionally 3) called bifurcation
branch extends and bifurcates again in a reiterative process
caused by an exogenously localised source of GDNF
How is the ureteric bud tip domain formed?
ret signalling mediates rearrangement of epithelial cells before budding to form domain
What signal induces mesenchymal-to-epithelial transition (MET) in the metanephric mesenchyme?
Wnt9B, which is secreted from the ureteric bud (paracrine signal)
What does Wnt4 do in the MM?
acts in an autocrine manner to propagate mesenchymal aggregation
renal vesicle continues to grow until Wnt4 concentration threshold is detected by quorum sensing
only then does RV begin to differentiate
What are some aspects that develop during MET of the MM in the kidney?
- generation of a tubular shape which form a lumen (single cell layered, non-stratified epithelium)
- development of adhesion junctions (cells stick together)
- establishment of apicobasal polarity
- development of occluding junction (prevents leaking of tubes)
What is a chemoattractant and a what is a chemorepellent?
chemoattractant - cells move toward a signal soure (up conc gradient)
chemorepellent - cells move away from a signal source (down conc gradient)
Name the main sections of the nephron and state their function.
glomerulus - blood filter
proximal tubes - recovery of salt, water, metabolites
loop of Henle - essential in producing (more concentrated urine)
distal tubes - K+, Na+, Ca2+ regulation
What is the mechanism of glomerulus development?
endothelial cells respond to a signal from vascular endothelial growth factor (VEGF) secreted by podocyte precursor cells
VEGF is a chemoattractant
What two methods are used to shape an organ?
- regulate orientation of cell division during organ growth (anisotropic growth)
- organ shape is sculpted by cell rearrangement (eg cell intercalation)
What is an example of anisotropic growth in renal tubes?
tubules increase in length not diameter, suggests specific orientation of cell division
defects in division lead to formation of cysts
What is an example of cell rearrangement in renal tubes?
highly ordered cell intercalation increases tubule length and decreases tubule circumference
Which tissue secretes GDNF?
Metanephric mesenchyme
What are the steps of nephron development?
-MM cells condense around UB
-Transform into small cysts with epithelial characteristics (renal vesicle)
-Differentiation and morphogenesis, fuses with UB
-Blood vessel progenitors invade and form glomerular capillaries
-Nephron differentiation (specialised transporting segments)
