Download Urinary development Function: excretion of metabolic waste

Urinary development
Function: excretion of metabolic waste, especially nitrogenous waste-10% ammonia,
urea (less toxic and concentrated-less water)
-Before birth- copious dilute urine, after birth loops of Henle lengthen and urine
becomes more concentrated.
-intermediate mesoderm gives rise to nephric lineage- suprarenal glands, gonads,
genital duct
1) Development of the three nephric systems
-Intermediate mesoderm gives rise to 3 embryonic kidney structures which develop
in a craniocaudal sequence
-Pronephros, mesonephros, metanephros
-These systems are developmentally distinct in two ways: temporally (as they grow
and regress at different times) and spatially (as they are confined to different
regions along the AP axis)
- Regression of the pronephros and mesonephric renal corpuscles generates the
non-segmental adult organ
Experimental
-Pax 2-transcription factor- expressed in nephrogenic intermediate mesoderm potent initiator of nephron development- ectopic nephric structures induced in non
nephrogenic regions, anywhere in the intermediate mesoderm when expressed by
viral transfection of mesoderm in chick embryos
-expression of Pax2 could be due to signalling factors released from somites and
ectoderm- when separated decreased gene expression
- KO of Pax2 in mice still form a mesonephric duct in pronephric and mesonephric
region but doesn’t grow into the metanephric region-so metanephric kidney
doesn’t develop. However when there is double KO out of both Pax2 and Pax8,
There is no urinary system-redundancy in the system
Pax 2 mutations lead to renal coloboma, oligomeganephronia (fewer larger
nephrons)
The hypothesis that the above genes are essential in matching the development of
the urinary system to the position on the AP axis is further supported by the finding
that they are all found in concentration gradients along the axis.
Gradients of gene expression along the AP axis specify positional identity, allowing
renal structures to form topically. This ensures that the pronephros, mesonephros
and metanephros form in the correct sequence and location. Regression of the
pronephros and mesonephros result in the non-segmental adult organ, which
develops from the metanephros. Therefore although the adult kidney does not
appear segmented like the spine, this does not reflect its developmental origin.
a) Formation of Pronephros
-4th week- intermediate mesoderm along the 5th to 7th cervical axial levels- undergo
mesenchymal TO epithelial transformation which give rise to the mesonephric
ROD -appears as a pair of 2 solid longitudinal RODS
-rods grow in a caudal direction due to the proliferation and recruitment of cells at
the caudal ends
-The mesonpheric rod unites with the cloaca in the lumbar region- at which point
regulated apoptosis creates a lumen (canalises) which progresses cranially forming
the Mesonephric duct
-in the cervical region the rods induce adjacent intermediate mesoderm to
condense and form epithelial buds/balls (pronephros)- not functional, as they don’t
fuse with the mesonephric duct- become hollow and regress in a cranio caudal
sequence and are absent by day 28
b) Formation of the mesenophros
-Caudal to the pronephric region the mesonpheric duct-induces formation of about
40 mesonpheric tubules in craniocaudal succession- upper thoracic region to L3leads to mesonephros-as more caudal tubules differentiate, the more cranial ones
regress- so only about 20 mesonephroi-L1 to L3
-the mesoneprhic tubules differentiate into excretory units-Mesonpheric renal
corpuscles similar to a shortened version of the adult metanephric nephron with
medial end forming bowman’s capsule- wraps around a knot of capillaries called a
glomerulus to form the renal capsule-lateral tip of each developing mesonephric
tubule fuses with Mesonephric duct- allows a passage from the excretory units to
the cloaca
-functional between 6-10 wks-blood supply from the paired dorsal aortae,
after 10 weeks they cease to function and regress- in females they
degenerate completely but in males the caudal most corpuscles contribute to
the genital duct system (Efferent ductules?)
c) Formation of the metanephros
-Development of metanephros begins at end of Wk 4 while mesonephros is
functional
-Definitive kidneys/Metanephroi- 2 functional components- excretory & collectingderived from different sources of intermediate mesoderm-Reciprocal induction
-at the caudal end the mesonpheric duct is induced to form the ureteric bud-forms
in the intermediate mesoderm of the sacral region- becomes the URETER
-each ureteric bud penetrates sacral intermediate mesoderm metanephric
blastema- metanephric mesenchyme induces the urteric bud to grow and birfucate
-When the ureteric bud first contacts the metanepheric blastema- tip
expands to form the initial ampulla that gives rise to the renal pelvis. 6TH WEEKthe ureteric bud bifurcates 4 times yielding 16 branches- these branches coalesce
to form 4 major calyces. 7TH WEEK- next 4 generations of bifurcations fuse forming
the minor calyces- 32nd WEEK-11 addittional generations of bifurcation- become
the future collecting ducts
-Branching of the ureter duct can be visualised by the use of Hoxb7/GFP transgene
to visualise UB branching morphogenesis
If the ureteric bud bifurcates prematurely (could be because blastema is further
away)- Y shaped bifid ureter- muscular walls contract asynchronously- so urine may
reflux from one branch into the other- stagnation of the urine-infections of the
ureter
Factors expressed in the metanephric mesoderm that regulate induction of budding
and branching of the ureteric bud-Key signalling factor is Gdnf found in
METANEPHRIC MESENCHYME is a ligand of the receptor Ret, Gfra expressed in
the mesonephric duct
Evidence: Misexpression of GDNF elsewhere in the intermediate mesoderm is
sufficient to induce ectopic ureteric buds, mice deficient in RET/GDNF- bilateral renal
agenesis
Caudal positioning of the ureteric duct- due to inhibitory factors released elsewhere
in the mesoderm, repressing induction in the more cranial regions- E.g BMP4 inhibits
RET signalling. BMP4 signalling molecule deficient mice develop ectopic ureteric
buds and double ureters
-As ureteric bud grows and branches into metanephric mesoderm it induces
mesenchyme to condense around the tips of the ureteric branches/ampulla and
form a metanephric blastemal cap
- the ampulla of the collecting tubule induces the metanephric blastemal capwhich initially is mesenchyme surrounded by extracellular matrix to becomes
reoorganised into an epithelial vesicle- increased gene expression of E-CADHERIN
-cap differentiates into a nephric vesicle.