Molecular mechanisms of kidney development

The differentiation of the kidney is conditioned by the interaction of the epithelium of the ureteral bud and the mesenchyme of the metanephrogenic blastema.

Mesenchyme action of metanephrogenic blastema
The mesenchyme, which also forms the cap above the peripheral end of the ureteral bud, expresses the transcription factor WT1 (protein with a zinc finger motif), which allows the metanephrogenic tissue to respond to the inductive influence of the ureteral bud epithelium. At the same time, WT1 influences the production of glial neutrophil factor (GDNF) and hepatocyte growth factor (HGF). These 2 growth factors are responsible for stimulating growth and branching of the ureteric bud.

The mesenchyme of the metanephrogenic blastema will later become the basis of the nephron. Its transformation into nephron epithelium is caused both by the expression of PAX2 and WNT4, which is conditioned by the expression of WNT6 and WNT9b in the ureteral bud, and by a change the composition of the extracellular matrix, which is also affected by the ureteral bud and where fibronectin, collagen 1 and 3 are replaced by collagen 4 and laminin. The synthesis of CAMs (Cell Adhesion Molecules) is also necessary for the transformation of mesenchyme into epithelium.

Action of the epithelium of the ureteral bud
The epithelium of the ureteral bud originates from the mesonephros. It arises from the ductus mesonephricus and sinks into the tissue of the metanephros. It synthesizes 2 tyrosine kinase receptors that participate in the signaling pathway between the ureteral bud and the mesenchyme of the metanephrogenic blastema.
 * RET for GDNF,
 * MET for HGF.

The epithelium of the ureteral bud, in addition to the above WNT6 and WNT9b, expresses 2 other growth factors: Both FG2 and BMP7 promote proliferation of the metanephros mesenchyme, thereby maintaining WT1 production.
 * Fibroblast growth factor 2 (FGF2),
 * Bone morphogenetic protein 7 (BMP7).

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