Abstract

The formation of the metanephric kidney begins with the protrusion of the ureteric bud from the caudal region of the nephric duct and its outgrowth into a loose group of nearby cells termed the metanephric mesenchyme. The development of the collecting system of the kidney can be artificially divided into three stages that include the initial outgrowth of the ureteric bud at a defined site on the nephric duct, the invasion of the bud into the metanephric mesenchyme, and the branching of the UB within the metanephric mesenchyme to form the individual collecting ducts. As the ureteric bud (UB) elongates and branches to become the collecting system of the kidney, the loose collection of the cells surrounding the caudal nephric duct condenses around the tip of the invading UB to form the metanephric cap. Some of these cells proliferate and migrate with the invading UB tips, while others remain in place and differentiate into connective tissue elements surrounding the stalk of the UB. One function of Six2 expression in these cells appears to be suppression of the epithelial differentiation signal provided by the UB. Apoptosis is a tightly regulated process during development, with expression of anti-apoptotic proteins such as Bcl-2 and Bcl-x(L) inhibiting cell death while proteins such as p53 and Bax promote cell death. Bcl-2 is found to be highly expressed in the metanephric mesenchyme in the regions undergoing condensation to form the renal vesicle, with lower expression in the uninduced mesenchyme and collecting system where apoptosis is more prominent.

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