1. UPREGULATION OF THE GDNF RECEPTORS IN THE ECTOPIC URETERIC BUDS INDUCED BY GDNF
- Author
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Hytonen, M. K., Sainio, K., and Sariola, H.
- Subjects
Neuroglia -- Research ,Kidneys -- Physiological aspects ,Embryology -- Research ,Biological control systems -- Analysis ,Biological sciences - Abstract
Glial-cell-line-derived neurotrophic factor (GDNF) belongs to the TGF-[Beta] super-family. It signals through Ret receptor tyrosine kinase and employs GDNF family receptor [Alpha]-1 (GFR[Alpha]-1) as a co-receptor. Gene targeted mice lacking GDNF or its receptors show severe defects in the enteric innervation, and they lack kidneys or show renal hypodysplasia. In nephrogenesis, GDNF and its receptors are required for the ureteric bud outgrowth and subsequent branching. GDNF-soaked agarose beads placed next to the Wolffian duct of E11 mouse embryo urogenitals induce ectopic budding from any segment of Wolffian duct. We have now studied the molecular characteristics of the GDNF-induced ectopic buds. Normally, when the ureteric bud is forming, the Ret expression is rapidly downregulated in the Wolffian duct and becomes restricted to the area of the presumptive ureteric bud. Later, Ret is expressed only by the tip of the bud. Whole mount in situ hybridization of the GDNF-bead-treated explants showed upregulation of the GDNF receptors by the ectopic buds. Moreover, Pax2 was expressed in this newly formed epithelia suggesting that the ectopic ureteric buds might be competent to induce nephrogenesis, if nephrogenic mesenchyme is transplanted to these sites.
- Published
- 2000