DIFFERENTIAL EXPRESSION OF NEUROTROPHIN RECEPTORS DURING RENAL DEVELOPMENT

Early kidney differentiation is driven by local cell-cell interactions . The metanephrogenic mesenchyme stimulates the epithelial ureter bud to grow and branch, whereas the ureter bud stimulates the mesenchyme t o convert into a new epithelium. These interactions may be dependent o n local growth factors and their receptors. We studied the expression of receptors for nerve growth factors during kidney development. Expre ssion of the low- and high-affinity receptors was cell-type specific. The low-affinity NGF receptor was found in the uninduced mesenchyme at early developmental stages, but in the glomerular podocytes at later developmental stages. In contrast, the high-affinity trkB receptor was found in the cortical mesenchyme cells that will differentiate into s troma. The trkC receptor was found only weakly expressed and in a few parts of the collecting ducts. The role of these receptors and c-ros, a receptor-type kinase expressed on the tip of the ureter bud, was stu died by modified antisense oligonucleotides. However, we found that bo th sense, antisense and nonsense phosphorothioate oligonucleotides inh ibited mouse and rat embryonic kidney development in vitro. The oligon ucleotides appeared to be toxic for rodent embryonic kidneys in the ex perimental conditions that we used. Moreover, oligonucleotides did not penetrate well into the epithelial sheets in the organ cultures. We c onclude that studies with phosphorothioate antisense oligonucleotide's in organ cultures of embryonic kidneys should be interpreted with cau tion. Our current data do not allow us to not assign a function for th e low- or high-affinity NGF receptors or c-ros in kidney development.