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<Title><![CDATA[HD6]]></Title>
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<PresenterName><![CDATA[cathy mendelsohn]]></PresenterName>
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<SlideText><![CDATA[nephrons in the kidney generate urine that is  propelled  to the ureters and then to the bladder for storage and excretion  ]]></SlideText>
<Notes><![CDATA[Kidney first 1 function for both]]></Notes>
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<SlideText><![CDATA[The Urinary outflow tract:  monitors and regulates extra-cellular fluids excretes harmful substances in urine, including nitrogenous wastes (urea) returns useful substances to bloodstream  maintain balance of water, electrolytes (salts), acids, and pH in the body fluids ]]></SlideText>
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<Title><![CDATA[Formation of Urine:]]></Title>
<SlideText><![CDATA[Formation of Urine: blood is filtered to  the glomerulus capillary walls are thin blood pressure is higher  inside capillaries than  in Bowman’s capsule COLLECTING  DUCT NEPHRON ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Formation of Urine:]]></Title>
<SlideText><![CDATA[Formation of Urine: nitrogen-containing waste products of protein metabolism, urea and creatinine, pass on through tubules to be excreted in urine urine from all collecting ducts empties into renal pelvis urine moves down ureters to bladder 	empties via urethra ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Formation of Urine:]]></Title>
<SlideText><![CDATA[Formation of Urine: in healthy nephron, neither protein nor RBCs filter into capsule in proximal tubule, most of nutrients and large amount of water reabsorbed back to capillaries salts selectively reabsorbed according to body’s needs water reabsorbed with salts ]]></SlideText>
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<SlideText><![CDATA[The urogenital system derives predominantly from  intermediate mesoderm ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<SlideText><![CDATA[During development, 3 successive kidneys form: Pronephros (head kidney) Mesonephros (middle kidney) Metanephros (definitive kidney) ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Slide 8]]></Title>
<SlideText><![CDATA[pronephros in an early embryo ]]></SlideText>
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<SlideText><![CDATA[Mesonephros in intermediate embryo ]]></SlideText>
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<SlideText><![CDATA[A metanephros is always drained exclusively by one duct, the ureter. In birds in reptiles the ureter separates from the nephric duct (Wolffian duct) and enters the cloaca. In mammals, the ureter separates from the nephric duct and enters the bladder ]]></SlideText>
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<SlideText><![CDATA[renal development begins when the ureteric bud invades  kidney mesenchyme (the metanephric blastema)  ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<SlideText><![CDATA[kidney ureter common  nephric duct Wolffian duct urogenital sinus trigone bladder urethra As the embryo grows, the ureters lengthen, and the kidneys rotate and ascend along the dorsal body wall  ]]></SlideText>
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<SlideText><![CDATA[Part I. Making a kidney Renal vein renal artery renal calyx medullary pyramid renal cortex segmental artery arcuate artery arcuate vein interlobar vein segmental vein renal column renal papilla renal pelvis ureter ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<SlideText><![CDATA[collecting ducts ureter branching ureteric  bud tips The distinct cellularity of the collecting duct system and ureter depends on developmental signals from surrounding mesenchyme  the collecting duct system and ureter are  derived from the ureteric bud ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<SlideText><![CDATA[Diverse cell types lining the nephron perform distinct functions ]]></SlideText>
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<SlideText><![CDATA[branching morphogenesis and nephron formation last until just after birth   occur exclusively in the peripheral domain beneath the renal capsule new generations of nephrons and ureter branches displace older generations inward  further differentiation occurs in inner domains at a distance from the renal capsule The kidney is radially patterned ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<SlideText><![CDATA[stroma nephron progenitors ureteric bud tips NEPHRONS COLLECTING DUCT SYSTEM CAPSULE/INTERSITIUM RECIPROCAL SIGNALING BETWEEN STROMA, NEPHRON PROGENITORS AND      URETERIC BUD TIPS GIVES RISE TO CELL TYPES IN THE MATURE KIDNEY ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<SlideText><![CDATA[shape changes and local proliferation at ureteric bud tips  			forms an ampulla Branching morphogenesis: ampullae form at ureteric bud tips a cleft forms  and the tips begin to bifurcate  the tips elongate new ampullae form   cleft stock tip ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<SlideText><![CDATA[The collecting duct system grows from the  periphery by dichotomous branching ub 2ndG 3rdG 4thG Wolffian duct at birth: day 1 ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Slide 20]]></Title>
<SlideText><![CDATA[ampulla  stalk Wolffian duct cleft Costantini Lab Columbia University, Dept. of Genetics & Development Branching morphogenesis in Real time ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<SlideText><![CDATA[NEPHRONS FORM EXCLUSIVELY AT URETERIC BUD TIPS IN RESPONSE TO  LOCAL SIGNALS FROM URETERIC BUD CELLS nephron progenitors ureteric bud tip ]]></SlideText>
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<Title><![CDATA[Slide 22]]></Title>
<SlideText><![CDATA[from "The Kidney: From normal development to congenital disease". 2003. Eds Vize, et al. nephron progenitors  stroma renal vesicle S-shaped body induction stroma Nephron renal vesicle comma-shaped body ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<SlideText><![CDATA[Nephron  progenitors condense at ub tips, aggregate and trans-differentiate into epithelial cells  that make up the renal vesicle, Comma and S-shaped bodies  from: The kidney: Eds, Vize et al., 2003) ]]></SlideText>
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<SlideText><![CDATA[Reciprocal Signaling is required for branching morphogenesis and  for nephron differentiation during renal development ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<SlideText><![CDATA[co-culture experiments demonstrate reciprocal 	signaling between ureteric bud epithelial and nephron progenitors nephron induction branching morphogenesis from: The kidney: Eds, Vize et al., 2003) ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Slide 26]]></Title>
<SlideText><![CDATA[no ureteric bud, nephron progenitors undergo apoptosis X from: The kidney: Eds, Vize et al., 2003) ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Slide 27]]></Title>
<SlideText><![CDATA[no nephron progenitors, no branching morphogenesis signals from the ureteric bud control nephron induction  signals from nephron progenitors control branching morphogenesis ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Slide 28]]></Title>
<SlideText><![CDATA[Ret mutations in humans cause renal abnormalities, Hirschsprung's disease and cancer  RET-GDNF SIGNALING EXEMPLIFIES A RECIPROCAL EPITHELIAL-MESENCHYMAL  PATHWAY THAT IS CRUCIAL FOR RENAL DEVELOPMENT ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Slide 29]]></Title>
<SlideText><![CDATA[Mutations in Ret, Gdnf or Gfra1 result in renal agenesis or hypoplasia ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Slide 30]]></Title>
<SlideText><![CDATA[URETERIC  BUD  Gdnf secreted by nephron progenitors binds to Ret via the Ret co-receptor (Gfra1) inducing branching morphogenesis Gdnf STROMA NEPHRON  PROGENITORS ? Ret/Gfra1 STROMAL CELL SIGNALS CONTROL RET EXPRESSION IN URTERIC BUD CELLS ]]></SlideText>
<Notes><![CDATA[Frnak’s lab]]></Notes>
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<Title><![CDATA[Slide 31]]></Title>
<SlideText><![CDATA[ub The Ret receptor is expressed in ureteric bud tips and controls branching morphogenesis ureteric bud (RET) stroma (vitamin A) Vitamin A from Stromal cells controls Ret expression in ureteric bud cells  Vitamin A deficiency generates renal malformations similar to those induced by Ret mutations ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Slide 32]]></Title>
<SlideText><![CDATA[BRANCHING MORPHOGENESIS STROMA NEPHRON  FORMATION FOXD1 MANY GENES ARE NOW KNOWN THAT REGULATE RENAL DEVELOPMENT WNT4 GDNF VITAMIN A ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Slide 33]]></Title>
<SlideText><![CDATA[Mouse models and human genetics have identified  genes that when deleted in humans result in renal abnormalities but in most cases,  the genetic basis of renal defects is still unknown ]]></SlideText>
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<Title><![CDATA[Slide 34]]></Title>
<SlideText><![CDATA[Part II. The lower urinary tract ]]></SlideText>
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<Title><![CDATA[Slide 35]]></Title>
<SlideText><![CDATA[nephrons in the kidney generate urine that is  propelled  to the ureters and then to the bladder for storage and excretion  ]]></SlideText>
<Notes><![CDATA[Kidney first 1 function for both]]></Notes>
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<Title><![CDATA[Slide 36]]></Title>
<SlideText><![CDATA[hydronephrosis in utero physical or functional blockage that impedes urine flow can cause renal scarring, hydronephrosis or end state renal disease ]]></SlideText>
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<Title><![CDATA[Slide 37]]></Title>
<SlideText><![CDATA[proper positioning of the ureter orifice is necessary for: formation of patent connections along the outflow tract preventing reflux  X obstruction reflux normal ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Slide 38]]></Title>
<SlideText><![CDATA[sprouty, slit-2, retinoid excess vitamin A deficiency, Ret  Calcineurin B (peristalsis)  sonic hedgehog (muscle) uroplakin (epithelium) abnormal position of the ureter orifice abnormal peristalsis Physical vs Functional obstruction ]]></SlideText>
<Notes><![CDATA[]]></Notes>
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<Title><![CDATA[Slide 39]]></Title>
<SlideText><![CDATA[The urogenital sinus forms the bladder and urethra in both sexes  The urorectal septum partitions the cloaca ("sewer") into the urogenital sinus (ventral) and hindgut (dorsal) Larsen's Embryology, 6th Edition cloaca urachus hindgut urorectal septum from: The kidney: Eds, Vize et al., 2003) ]]></SlideText>
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<SlideText><![CDATA[ The mesonephric duct (aka Wolffian duct) forms the vas (ductus)    deferens, seminal vesicle and epididymis in males  Mullerian ducts (paramesonephric ducts) degenerate in females The urogenital sinus forms the bladder, urethra (including the    prostate and penis) from: The kidney: Eds, Vize et al., 2003) ]]></SlideText>
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<SlideText><![CDATA[in females the urogenital sinus forms the bladder,   urethra and vagina Wolffian (mesonephric ducts) regress Mullerian (paramesonephric ducts) differentiate   into the uterus and upper vagina from: The kidney: Eds, Vize et al., 2003) ]]></SlideText>
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<SlideText><![CDATA[The trigone is defined as the portion of the urogenital sinus that lies between the ureters and sex ducts  Urine transport depends on proper connections between the  ureters and the bladder trigone after: Hutch, J.A. Anatomy and physiology of the bladder, trigone and urethra, xv, 180, [2] p. (Butterworths Appleton-Century-Crofts, London, New York,, 1972). ]]></SlideText>
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<SlideText><![CDATA[The trigone is a region where the detrusor and urethral  	    muscle join the ureteral fibers detrusor urethral  muscle ureter  sheath ureter bladder proper configuration of  muscle groups that form the  trigone  is likely to be important for urinary tract function ]]></SlideText>
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<SlideText><![CDATA[the flap valve is part of the trigone and is an anti-reflux mechanism that prevents urine back flow (reflux) smooth muscle actin ureter epithelium muscle ureter intra-mural ureter Flap-valve function depends on insertion of the ureter orifice at the proper position in the bladder neck (trigone) intra-mural  ureter  extra-mural ureter detrusor sheath ]]></SlideText>
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<SlideText><![CDATA[kidney ureter common  nephric duct Wolffian duct urogenital sinus trigone bladder urethra THE TRIGONE IS MORPHOGLOGICALLY DISTINCT FROM THE BLADDER AND IS THOUGHT TO BE DERRIVED FROM THE COMMON NEPHRIC DUCT  ]]></SlideText>
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<SlideText><![CDATA[The Bladder  The bladder epithelium is lined with  plaques made from uroplakins that form a water-proof barrier smooth muscle of the detrusor and rugae (folds) in the urothelium 	 allow the bladder to expand and contract Detrusor muscle urothelium ureter rugae ]]></SlideText>
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<SlideText><![CDATA[smooth muscle actin uroplakin a transitional epithelium expressing uroplakin also lines the ureters The ureter smooth muscle coat mediates myogenic peristalsis defective smooth muscle formation or mutations in     uroplakins cause functional obstruction ]]></SlideText>
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<Title><![CDATA[Slide 48]]></Title>
<SlideText><![CDATA[URETER PERISTALSIS IN VITRO (E15 mouse embryo):  J. Clin. Invest. 113:1051-1058 (2004).  Ching-Pin Chang, et al.  kidney ureter bladder Impaired peristalsis is a cause of obstruction (functional obstruction) ]]></SlideText>
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<Title><![CDATA[Slide 49]]></Title>
<SlideText><![CDATA[kidney ureter common  nephric duct Wolffian duct urogenital sinus trigone Mature connections are established when the ureter orifice is transposed from the posterior Wolffian duct (the common nephric duct) to the bladder  bladder urethra The ureter is initially joined to the Wolffian duct (future vas-deferens) not to the bladder  ]]></SlideText>
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<Title><![CDATA[Slide 50]]></Title>
<SlideText><![CDATA[How do ureters move from the Wolffian duct to the bladder? ]]></SlideText>
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<Title><![CDATA[Slide 51]]></Title>
<SlideText><![CDATA[Trigone common nephric duct during ureter transposition, the cnd is incorporated  into the bladder  where it expands to form the trigone effectively separating the ureter orifice from the Wolffian duct According to the accepted model, trigone formation is  considered to be crucial for repositioning the ureter orifice ]]></SlideText>
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<Title><![CDATA[Slide 52]]></Title>
<SlideText><![CDATA[Accepted model of ureter transposition formation of the trigone from the common nephric duct repositions the ureters in the bladder Larsen's Embryology ]]></SlideText>
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<Title><![CDATA[Slide 53]]></Title>
<SlideText><![CDATA[kidney ureter Wolffian  duct common nephric duct  expression of Jelly Fish green fluorescent protein in the mouse common nephric duct of this transgenic mouse enables us to follow its fate during ureter insertion using mouse models to re-assess the mechanism of  ureter transposition: ]]></SlideText>
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<Title><![CDATA[Slide 54]]></Title>
<SlideText><![CDATA[The common nephric duct appears to regress rather than expand what happens to the common nephric duct during ureter transposition? ]]></SlideText>
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<Title><![CDATA[Slide 55]]></Title>
<SlideText><![CDATA[Ureter transposition depends on apoptosis of the  common nephric duct apoptotic common  nephric duct cells ]]></SlideText>
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<Title><![CDATA[Slide 56]]></Title>
<SlideText><![CDATA[A revised model of ureter transposition apoptosis of the common nephric duct enables the ureter orifice to detach from the Wolffian duct   the common nephric duct is absorbed into the expanding  urogenital sinus. The ureter makes direct contact with and inserts into the urogenital sinus  continued growth and expansion of the urogenital sinus  moves the ureter orifice further anterior to the bladder neck ]]></SlideText>
<Notes><![CDATA[Old model]]></Notes>
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