Renal Embryology PDF

Urinary System Embryology Thomas Gould, PhD Associate Professor UNSOM, PCB CMM 202 [email protected] Reading: Langman’s Medical Embryology, Chapter 16, 1st half ...

Urinary System Embryology Thomas Gould, PhD Associate Professor UNSOM, PCB CMM 202 [email protected] Reading: Langman’s Medical Embryology, Chapter 16, 1st half  Learning Objectives Describe role of intermediate mesoderm in development of the urinary system. Define: nephron, glomerulus, renal corpuscle, urorectal septum, pronephros, mesonephros, and metanephros. List the derivatives of the ureteric bud and the metanephric mesoderm. Understand the importance of mesenchymal-epithelial transitions in kidney development. Describe the formation of the urinary bladder and the urogenital sinus. Describe the embryonic origins of renal agenesis, congenital cystic kidney, double ureter, horseshoe kidney and bladder exstrophy.  Germ Tissues: Mesoderm The chordamesoderm and paraxial mesoderm form the axial skeleton, whereas the intermediate mesoderm forms the kidneys and gonads, and the lateral plate mesoderm forms the circulating systems, body wall, and limbs (except for the musculature). nt neural tube. This figure is a modified version of an image from Gilbert, SF & Barresi, MJF. Developmental Biology, 2019  Embryonic Renal Origins Kidney develops from intermediate mesoderm Also called nephrogenic cord Kidney develops in a cranio-caudal gradient 21d 25d  Embryonic Renal Origins Intermediate mesoderm Same mesodermal ridge gives rise to urinary and genital systems “Urogenital ridge”  Renal Development 3 kidneys in overlapping succession: “Holonephros” Pronephros Cervical region, nonfunctional, forms at start of GW4 and regresses by GW5 Mesonephros Thoracolumbar region, transiently functional, appears at 4th week and disappears by end of 2nd month (except for mesonephric duct in males) - “transitory kidney” Metanephros Sacral or pelvic region, also appears in 5th week – “definitive kidney” 1 2 3 GW4 GW5  Pronephros Appears during GW4 and disappears by GW5 Pronephros in neck region From nephrogenic cord (1) Only until 13th /14th somite Then, renal primordia are considered “mesonephros (1+2)” Divides into nephrotomes (5) Segmented masses of cells Includes both glomeruli and pronephric tubules 1 Nephrogenic cord 2 Mesonephric duct (Wolff) 1+2 Mesonephros 3 Intestinal tube 4 Cloaca 5 Nephrotomes 6 Yolk sac (umbilical vesicle) 7 Allantois 8 Outflow of the mesonephric duct into the cloaca http://www.embryology.ch/an glais/turinary/devebauche01. html#introduction  Pronephros Appears during GW4 and disappears by GW5 Pronephros in neck region (nephrotomes) Primitive glomerulus (2) Filtration unit Pronephric Tubules (1) Opens directly into intra-embryonic coelom (6) Pronephric Duct Not functional Serves as anlage of mesonephric duct Transient and non-functional structure 1. Pronephric tubule Atrophies and disappears during GW5 2. Glomerulus 3. Dorsal aorta 4. Splanchnic mesoderm 5. Somatic mesoderm 6. Intraembryonic cavity 7. Neural tube 8. Yolk sac 9. Endoderm http://www.chronolab.com/atlas/ embryo/pronephros.htm  Mesonephros Appears during GW4… Dorso-thoracolumbar region Also from nephrogenic cord (1 in left) Has its own nephron (3 in right) and tubules (5 in right) and duct (4 in right) Mesonephric tubules Lengthen and form an S-shaped loop First excretory tubules (pronephric not functional) Mesonephric (Wolffian) duct Collecting duct into which tubules enter – dorsal and lateral (2 in left, 4 in right) Empties urine into cloaca  Mesonephros Also: Paramesonephric (Mullerian) duct Not from mesonephros; derived from coleomic epithelium of intermediate mesoderm No renal function; rather reproductive  Mesonephros …Mostly disappears after GW8-10 Except: Mesonephric ducts Anlage of male reproductive structures Degenerate in female Analogous to: Paramesonephric ducts Anlage of female reproductive structures Degenerate in male  Metanephros Appears during GW5; Functional by GW10 Ureteric Bud Also called metanephrogenic diverticulum Outgrowth of mesonephric ducts Penetrates and induces differentiation of metanephric blastema  Collecting System Ureteric bud subdivides for 12 Generations 1-3 million Collecting Tubules – drain glomeruli Major and Minor Calyces – points of convergence for collecting tubules Renal Pelvis – point of convergence for 2-3 major calyces Ureter – major funnel delivering urine to bladder  Color Scheme I’ve used initial 3 colors until now Pronephros Mesonephros Metanephros Now we change: Mesonephros-derived structures like ureteric bud/collecting ducts = yellow Metanephros-derived structures like nephron = blue  Filtering System Metanephric blastema Primordial metanephric mesoderm Initially exists as: Undifferentiated tissue caps Induced by ureteric bud to form: Renal vesicles Finally develops into: Nephron  Filtering System Nephron (excretory unit) Renal Corpuscle Glomerulus - Tufted capillaries Bowman’s capsule - Membranous - surrounds glomerulus Renal Tubules Proximal convoluted tubule Loop of Henle Distal convoluted tubule Connect to collecting ducts Formed until birth; ~1e6 Urine production by GW10  Filtering System Derivation Nephron (renal corpuscle; renal tubules) From metanephros (metanephric mesoderm) (metanephric blastema) Collecting duct system (ureter, pelvis, calyx…) From ureteric bud which itself is derived from mesonephros (Wf duct)  Molecular Signals WT1 Gene Expressed in mesenchyme of metanephric mesoderm Maintains competence to respond to inductive cues from ureteric bud Wilm’s tumor – WT1 gain-of-function mutation Most common pediatric renal tumor; Incidence = 1/10,000 Heterogeneous; derived from mesenchymal stem cell?  Molecular Signals Mesenchyme of metanephric mesoderm Sends signals to ureteric bud epithelium Glial-derived Neurotrophic Factor (GDNF) – stim RET tyrosine kinase receptor on bud Hepatocyte Growth Factor (HGF) – stim MET tyrosine kinase receptor on bud Stimulates branching and dividing of the ureteric buds http://www.ncbi.nlm.nih.gov/books/NBK10089/  Molecular Signals Ureteric bud in turn signals to metanephric mesoderm Bone morphogenetic-related protein 7 (BMP7) & Fibroblast growth factor 2 (FGF2) Stimulates proliferation and blocks cell death of mesenchyme Wingless-related integration site 6 and 9b (WNT6 and WNT9b) Activates PAX2 expression Induces mesenchyme to condense around a lumen and form renal epithelium “Mesenchymal Epithelial Transition” Activates WNT4 expression Induces filtration tubule formation of this renal epithelium Epithelial basal lamina  Renal Agenesis Many Genes Including WT1 & GDNF loss-of-function mutations http://emedicine.medscape.com/article/983477-overview#a5 Potter Sequence / Syndrome – 1/10,000 Anuria, oligohydramnios, pulmonary hypoplasia Fetal urinary output regulates amniotic fluid volume Swallowed amniotic fluid contributes to lung development Neonatal death by hypoplastic lung From oligohydramnios, not anuria itself Leads to in utero compression Flattened face (Potter facies) Often (85%) presents with other severe defects Clubbed feet Cranial anomalies Skin fold from medial canthus across cheek Parrot beak nose Low-set ears Redundant skin Oligohydramnios =