Molecular Regulation Of Kidney Development

As with most organs, differentiation of the kidney involves epithelial mes-enchymal interactions. In this example, epithelium of the ureteric bud from the mesonephros interacts with mesenchyme of the metanephric blastema (Fig. 14.7). The mesenchyme expresses WT1, a transcription factor that makes this tissue competent to respond to induction by the ureteric bud. WT1 also regulates production of glial-derived neurotrophic factor (GDNF) and hepatocyte growth factor (HGF, or scatter factor) by the mesenchyme, and these proteins stimulate growth of the ureteric buds (Fig. 14.7A). The tyrosine kinase receptors RET, for GDNF, and MET, for HGF, are synthesized by the epithelium of the ureteric buds, establishing signaling pathways between the two tissues. In turn, the buds induce the mesenchyme via fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-7 (BMP-7) (Fig. 14.7A). Both of these growth factors block apoptosis and stimulate proliferation in the metanephric mesenchyme while maintaining production of WT1. Conversion of the

Metanephric tissue caps

Figure 14.7 Genes involved in differentiation of the kidney. A. WT1, expressed by the mesenchyme, enables this tissue to respond to induction by the ureteric bud. GDNF and HGF, also produced by the mesenchyme, interact through their receptors, RET and MET, respectively, in the ureteric bud epithelium, to stimulate growth of the bud and maintain the interactions. The growth factors FGF2 and BMP7 stimulate proliferation of the mesenchyme and maintain WTi expression. B. PAX2 and WNT4, produced by the ureteric bud, cause the mesenchyme to epithelialize in preparation for excretory tubule differentiation. Laminin and type IV collagen form a basement membrane for the epithelial cells.

Metanephric tissue caps

Wt1 Gdnf And Hgf

Figure 14.7 Genes involved in differentiation of the kidney. A. WT1, expressed by the mesenchyme, enables this tissue to respond to induction by the ureteric bud. GDNF and HGF, also produced by the mesenchyme, interact through their receptors, RET and MET, respectively, in the ureteric bud epithelium, to stimulate growth of the bud and maintain the interactions. The growth factors FGF2 and BMP7 stimulate proliferation of the mesenchyme and maintain WTi expression. B. PAX2 and WNT4, produced by the ureteric bud, cause the mesenchyme to epithelialize in preparation for excretory tubule differentiation. Laminin and type IV collagen form a basement membrane for the epithelial cells.

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