Organogenesis Flashcards
What is the definition of a mature organ?
intricately organised collection of cells with specialised activities that function collectively to execute vital bodily functions
What is organogenesis?
how organs ovult in development focusing on kidney. from undifferentiated cells to mature organ
What is the building block of the kidney?
- nephron and collecting duct
Regionalisation of the mesoderm:
- ___mesoderm (will be separated into blocks and make somites – skeletal muscle)
- ___mesoderm generates the kidney and gonads
- ___ mesoderm (generates circulatory system – heart, blood vessels etc.)
paraxial, intermediate, lateral plate
First step in kidney differentiation we need 3 genes to be activated. What are they?
Lim-1 (homeodomain TF)
Pax2 & Pax8 (paired box TF)
2nd step kidney specification. What is involved?
2 signals
- one from adjacent paraxial mesoderm
- one from lateral side of embryo
What type of signalling are these 2 signals?
Paracrine
Bone morphogenetic protein 2 (BMP2) is a secreted morphogen that directs different cell fates according to concentration. What level induces kidney tissue?
- Kidney tissue induced at ‘medium level’ of BMP2 activity
How cells self-organise to make a kidney? i.e internal conversations between tissues
Local reciprocal inductive interactions between the UB and MM drives kidney development
Within the intermediate mesoderm population of cells – 2 distinct cell types emerge: ureteric bud (UB) and the metanephric mesenchyme (MM)
2 populations of cells communicating between tissues to drive kidney development.
What is induction?
- Induction - one cell (inducer) regulates the behaviour of another cell (responder)
- The inducer sends a signal that the responder must be competent to ‘see’ and act on
What is reciprocal induction?
a dialogue or two-way conversion between the two different populations of cells
Provides a mechanism by which different tissues that contribute to the same organ can grow and develop in a coordinated way – growth and development is proportionate
2 mismatches that forms if UB and MM didn’t have reciprocal induction:
mismatch in ratio/co-ordination
How does the transfilter induction assay show the communication between UB and MM?
MM and UB separated and then put together which lead to UB branching and nephron formation.
- they have to be close together to have ‘conversation’ proves the crosstalk
- This suggests the ureteric bud and the metanephric mesenchyme are talking to one another
How does the branching of the ureteric tree occur? in relation to Ret/GDNF signalling
GDNF is secreted by MM and is recognised by Ret receptor present in nephrite duct and tips of ureteric branches.
What does removing GDNF and no branching show?
GDNF signals is necessary for branching
What does ectopic GDNFand extra branching show?
GDNF signalling is sufficient for budding/branching
Branching behaviours require Ret receptor activity. relative levels of Ret determines the branching populations. cells with higher ret activity exhibit ____
Stronger branching behaviours
What cellular behaviours drive branching?
- differential cell proliferation
- cell rearrangement
- localised remodelling of ECM
Describe the differential proliferation in UB
tip cells proliferate more than trunk cells. differential cell proliferation contributes to branching.
Describe the cell rearrangement of epithelial cells
ret signalling mediates rearrangement of epithelial ells before budding to form the UB tip domain
How does ECM influence branching patterns? In relation to collagen 18
Collagen 18 is expressed in trunk but not tip. GDMP represses collagen 18 at tip
Overview of nephron development:
1. ___ cells condense around ___
2. transform into small ___ with epithelial characteristics (renal vesicles) - ______l transition (MET)
3. ______ and ______ fuses with UB
4. blood vessel progenitors invade and construct glomerular capillaries
5. nephron ______ e.g. specialised transporting segments of the nephron
- metanephric mesenchymal
- Ureteric bud
- cysts
- mesenchymal to epithelial
- differentiation
- morphogenesis
- differentiation
Transfilter induction assay shows that isolated MM dies and MM with UB forms nephron after MET. what does this show?
signal from UB is needed for the survival and MET of MM
in MET ____ is secreted from ___ which induces MET in ___
- Wnt (9B)
- UB
- MM
Renal vesicle size is approximately equal. how is the size measured?
Wnt9B induces Wn4 expression within MM
- acts in autocrine manner to propagate mesenchymal aggregation
- continuous to grow by recruiting more MM until threshold is reached (quorum sensing)
During MET how are epithelial characteristics developed?
- tubular shape and form single cell layered lumen
- develop adhesion junctions
- establish apicobasal polarity
- occluding/tight junctions
From proximal to distal, how is the pattern formation and regional differentiation in the nephron established?
Distal proximal gradient of gene activity. morphogenic signalling from UB. high conc = distal, low conc = proximal
How did the glomerular capillaries develop?
migration of endothelial cells into developing glomerulus
How do endothelial cells know where to migrate to?
Podocyte precursor cells secrete a signal to induce endothelial migration into developing glomerulus. Endothelial cells move up the signal gradient (chemotaxis)
What is chemoattractant ?
cells move toward a signal source up the conc gradient
What is chemorepellent?
cells move away from signal source (down the conc gradient)
What is the function of Vascular Endothelial Growth Factor (VEGF)
- expressed n secreted from the inner cup of developing nephron
- Endothelial cells are competent to respond to signal because they express the VEGF receptor on their surface
- VEGF = a chemoattractant
How does the polycystic kidney disease lead to kidney failure?
- Progressive formation of large fluid-filled cysts
- Increase in tubular diameter
2 ways to shape an organ:
(1) oriented cell division during organ development (anisotropic growth)
(2) cell intercalation = Organ shape is sculpted by cell rearrangement
explain the oriented cell division in renal tubules
- ubules increase in length, but not diameter
- Suggests: orientation of cells as they separate at division is aligned with long axis of tubule and not around circumferential axis
- Example of anisotropic growth - divide along one axis
What is the mitotic angle in polycystic mutant rodent?
random - abnormal tubule shape
Explain cell arrangement in renal tubules
- Rearrangement is driven by cell intercalation
- Highly ordered cell-intercalation increases tubule length and decreases tubule circumference
