Download Kidneys

The Origin of the
Kidneys: Evolution and
Development
Dr Mike Wride
School of Natural Sciences
Zoology Department
email: [email protected]
The kidneys?
• Kidney Function and Regulation: Physiology
(Dr. Alan Tuffery)
• Excretion of nitrogenous waste and
regulation of water balance
• Structure of the kidneys:
• A little Anatomy
• Embryological Origin
• Development
Topics to be covered in
today’s lecture
•
•
•
Kidney Anatomy
•
The 3 stages of kidney development: pronephros,
mesonephros and metanephros
•
Genes involved in metanephros (adult kidney)
development: animal models and congenital defects
Early development/gastrulation - a reminder
Lineages of mesoderm: kidneys from intermediate
mesoderm/interactions of mesoderm
Kidney anatomy
The Nephron
Useful Texts for Kidney
Development
• Developmental Biology 8th Ed. Scott S
Gilbert. Sinauer. Chapters 11 and 14
• Plumbing in the embryo: developmental
defects of the urinary tracts. Uetani N,
Bouchard M. Clin Genet. 2009 Apr;75(4):
307-17. Review. (Available through
PubMed: http://www.ncbi.nlm.nih.gov/sites/
entrez)
Early development: A
Reminder
Development of
the
Preimplantation
Blastocyst in
Mice from
Embryonic Day
0 (E0) Through
Day 5 (E5.0).
Tissue formation in the human
embryo between days 7 and 11
Gilbert Fig 11.33 p 353
A and B: Inner cell mass forms
epiblast and hypoblast.
C. Epiblast splits into the
amniotic ectoderm and the
embryonic epiblast. The adult
mammal is formed from the
cells of the embryonic
epiblast.
D. The extraembryonic
ectoderm forms the yolk sac.
A Reminder: Early
Development
• "It is not birth, marriage, or death,
but gastrulation which is truly the
most important time in your life."
- Prof Lewis Wolpert
Gastrulation
• Gastrulation begins between days 14 and
16 of human development and at about
E6.5 in the mouse
• Gastrulation results in formation of the 3
germ layers: mesoderm (e.g. muscle, bone,
kidneys), endoderm (e.g. gut) and ectoderm
(e.g. nervous system/epidermis)
Gastrulation Cont...
Figure 11.34. Gilbert Chapter 11, page 354
•
Mesoderm forms: Chordamesoderm (notochord),
paraxial mesoderm (somites) and lateral plate mesoderm
•
Kidneys are derived from intermediate mesoderm
(also reproductive organs)
Major lineages of mesoderm
Figure 14.1 Gilbert p 444
The
Urogenital
system
Signals from the paraxial
mesoderm “induce”
pronephros formation in
the intermediate
mesoderm (chick embryo)
Surgical separation of paraxial
mesoderm from intermediate
mesoderm on one side of
embryo. As a result, no
kidney formed on that side.
3 Stages of Development
of Mammalian Kidney
•
Stages 1 and 2 are transient, Stage 3 is the
formation of the adult kidney
•
Stage 1: Pronephric duct arises in intermediate
mesoderm ventral to anterior somites. Cells of
duct migrate caudally (towards the tail) and induce
the adjacent mesenchyme to form the tubules of
the initial kidney: the pronephros. In mammals,
anterior (rostral) portions of the pronephric duct
and tubules degenerate, while caudal portions
persist and serve as central component of
excretory system throughout its development
(Wolffian Duct).
3 Stages of Development of
Mammalian Kidney Cont...
• Stage 2: Formation of Mesonephros.
Middle portion of nephric duct induces a
new set of kidney tubules in adjacent
mesenchyme (called the mesonephros). In
humans, has a brief existence (cells die by
programmed cell death; apoptosis), but is a
source of blood stem cells and
mesonephric tubules form sperm carrying
tubes in amniote males.
3 Stages of Development
of Mammalian Kidney
•
Stage 3: Formation of the Metanephros
(permanent kidney): formed by interactions between
epithelial and mesenchymal components of
intermediate mesoderm. Metanephrogenic
mesenchyme induces ureteric buds (will form
collecting ducts and ureters), which then interact
with the metanephrogenic mesenchyme to cause it
to condense around them to form the nephrons. In
turn induces branching/growth of the ureteric buds.
RECIPROCAL TISSUE INTERACTIONS AND
INDUCTION
14.21 General scheme of development in the
vertebrate kidney
14.21 General scheme
of development in the
vertebrate kidney
14.22 Reciprocal induction in the development of the mammalian kidney
14.23 Kidney induction observed in vitro
Formation of
Metanephros: A Dialogue
?????
Ureteric Bud
Metanephrogenic
Mesenchyme
?????
The Kidney is an Important Model for
Organogenesis
Paracrine and Autocrine Factors
Regulate Kidney Development
•
Transcription Factors: Forkhead winged helix
TFs (Foxes), Homeobox genes (Pax2, Hox11)
•
Growth Factors: Fibroblast growth factors
(FGFs), Wnts, BMPs, GDNF
•
Tumour suppressors: Wilm’s tumour 1
(WT1)
•
Importance indicated by Knockout mouse studies
and in congenital defects (absent or rudimentary
kidneys; congenital tumours)
Transcription Factors:
Homeobox genes
Growth Factors: FGFs
Growth
Factors:
Wnts
Growth Factors: BMPs
Growth Factors: GDNF
Different Factors Act at Different
Steps of Adult kidney development
•
Step 1: Formation of Metanephrogenic
mesenchyme - Foxes, Hoxes and WT1
•
Step 2: Metanephrogenic mesenchyme secretes
GDNF to induce and direct the ureteric bud
•
Step 3: Ureteric bud secretes FGF2, BMP7 to
prevent mesenchymal apoptosis
•
Step 4: Wnt9B and Wnt6 from the ureteric bud
induce mesenchyme to aggregate
14.24 Ureteric bud growth is dependent on Glial cell
line-derived neurotrophic factor (GDNF) and its
receptors (Ret)
Ureteric bud
from Wild type
mouse
Mouse
heterozygous
for mutation
in GDNF
Mouse
homozygous
for mutation
in GDNF
72 Hr cultures of mouse ureteric bud
14.25 Wnts are critical for kidney development
Different Factors Act at Different
Steps of kidney development
•
Step 5: Wnt4 converts aggregated mesenchymal
cells into a nephron
•
Step 6: GDNF, Wnt11 and TGFb1 from the
mesenchyme induce branching of the ureteric bud
•
Steps 7 and 8: Differentiation of the nephron
and growth of the ureteric bud are dependent
upon Foxb2
•
Step 9: Insertion of the ureter into the bladder
Development of the Bladder and
its Connections to the Kidney via
the Ureter
Summary of Today’s
Lecture
•
•
•
Kidney Anatomy
•
The 3 stages of kidney development: pronephros,
mesonephros and metanephros
•
Genes involved in metanephros (adult kidney)
development: animal models and congenital defects
Early development/gastrulation - a reminder
Lineages of mesoderm: kidneys from intermediate
mesoderm/interactions of mesoderm