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Explore the congenital polycystic disease of the kidney, PKD mutations, and nephric system development with Cytokeratin immunostaining. Learn about the chronological order of Pro-, Meso-, and Metanephros development, ureteric bud growth, and nephron formation in embryos. Discover the crucial role of reciprocal inductive signals and GDNF expression in kidney maturation and cloacal region division.
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Epithelio-mesenchymal interaction: kidney development Dr. Nandor Nagy Semmelweis University, Budapest
Congenital polycystic disease of kidney (1:800 live birth), PKD1 and PKD2 mutation
Three sets of nephric systems: • Pronephros (Greek: first kidney)
2. Mesonephros • Functionbetweeweek 6-10. • Mesonephricnephronsdonotformany part of thematurekidney !
3. Metanephros (definitive kidney) Ureteric buds sprout out from the mesonephric ducts (E28) And penetrate into the metanephric blastema
CHRONOLOGICAL ORDER OF THE DEVELOPMENT OF PRO-, MESO- AND METANEPHROS 1. 2. 3. 4. Cytokeratin fluorescence immunostaining of mouse embryo. Cytokeratin is present in nephric duct and its derivates. 20. day of embryonic life 25. day of embryonic life 35. day of embryonic life
Ureteric bud Uretericbud – outgrowthfromthemesonephricductnearitsentranceintothecloaca • reciprocal induction -retinoic acid dependent • Cranial-caudal patterning establishes a “renogenic” region within the intermediate mesoderm in the tail of the embryo –this renogenic mesoderm is the METANEPHRIC BLASTEMA • The METANEPHRIC BLASTEMA secretes growth factors that induce growth of the URETERIC BUD from the caudal portion of the mesonephric duct. • The URETERIC BUD proliferates and responds by secreting growth factors that stimulates proliferation and then differentiation of the metanephricblastema into glomeruli and kidney tubules (i.e. induces the blastema to undergo mesenchymal-to-epithelial transition ).
Ureteric bud Ureteric bud - elongates and penetrates the blastema 1. Caudal part -the stalk develops to ureter -reciprocalinductivesignals!!! 2. Cranial part - undergoes a number of dichotomousbranchingevents to form the urinary collecting tubulesystem -thefirst 4 generations of tubulesenlargetoformthemajor calyces - second 4 generationsfusetoformtheminor calyces - the end of eacharchedtubuleinducesclustersofblastemacellstoformsmallmetanephricvesicles
Division of the cloacal region 5 weeks 6 weeks 8 weeks