To What Extent Is The Development Of The Kidney An Ideal Model To Study Epithelial Notes

To what extent is the development of the kidney an ideal model to study epithelial-mesenchyme interactions?

The kidney is an unusual organ in that it develops though three nephric systems, reflecting primitive systems which arose successively during evolution. These are the pronephros, the mesonephros and the metanephros; the metanephroi are regarded as the ‘definitive kidneys’ as they will go on to form the kidneys in the adult. The first appearance of the nephric systems is in the intermediate mesoderm at the level of C5-C7, where cells differentiate into epithelium in the 4^th week. These cells condense in the pronephros region into a pair of mesonephric or Wolffian ducts, and stimulate the formation of epithelial buds in the intermediate mesoderm medial to both mesonephric ducts. These buds are the pronephroi; they develop into functional kidneys in some lower organisms but in humans they regress by day 25 as the cranial end of the Wolffian ducts degenerate. By this time, however, the mesonephric ducts have grown caudally and induced mesodermal mesenchyme to form mesonephric tubules, the beginning of the mesonephros. The mesonephric tubules also undergo degeneration, in a cranial to caudal manner, so that the Wolffian ducts appear to shift towards the caudal end of the embryo, where the kidneys will eventually form so that they must ascend later in development. At the beginning of 6^th week, there are 20 pairs of definitive mesonephroi, which consist of functional glomeruli, Bowman’s capsules, tubules and other elements which will be present in the metanephros-derived adult kidney. Remarkably, these structures, which will begin to regress after 10 weeks, act as transient embryonic excretory units and produce urine, which passes through each mesonephric tubule to the mesonephric duct, the caudal tips of which have fused to the ventrolateral walls of the cloaca, thus forming an excretory route (this will eventually become the trigone of the bladder). The mesonephric duct remains in the female as the paroöphoron and epoöphoron, and in the male contributes to the genital system, particularly the vas deferens. On day 28, metanephros development begins with ureteric buds growing from the distal end of the mesonephric ducts. Within days these invade condensations of cells called the metanephric blastema, and ureteric bud bifurcation commences. The buds first form two lobes in 6^th week, and extensive branching leads to 1-3 million branches by 32^nd week¹. Initial branches of the bud coalesce to form the major then minor calyces, and the more distal buds form the individual nephrons; the initial ureteric bud ampulla becomes the renal pelvis. The metanephric blastema caps at the tips of the ureteric buds differentiate to epithelial cells, forming the Bowman’s capsule and proximal tubules of the nephron. The metanephric blastema tubule and ureteric bud fuse to form a continuous lumen, the uriniferous tubule, allowing urine produced to flow through the mesonephric ducts. The development of metanephric function is well timed as the first functional units appear around 10 weeks, as the mesonephroi start to degenerate^1,2; the embryo is therefore able to continuously filter blood and produce urine and amniotic fluid (the lack of which function results in Potter Syndrome). Metanephros development is complex in that there is reciprocal interaction between the mesenchyme and the epithelial ureteric bud; these signals control bud positioning and branching, and both tissues contribute to the final nephron and urine collecting system.

Epithelial-mesenchyme interactions are important in the development of the kidney as initiation of the various nephric systems depends upon complex signalling between different tissues such as the ectoderm, mesodermal mesenchyme and mesodermal epithelium. For example, the metanephric blastema dies if no ureteric bud induction takes place². Over 300 genes involved in specifying the developing kidney have been identified by methods including expression analysis and studies of transgenic mice. For example, mutations in Notch 2 result in underdeveloped glomeruli, whereas knockout GDNF mice do not develop ureteric buds and subsequently lack kidneys²; GDNF has...

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