Sulphated proteoglycan is required for collecting duct growth and branching but not nephron formation during kidney development.
Kidney epithelia have separate origins; collecting ducts develop by ureteric bud growth and arborisation, nephrons by induced mesenchyme-epithelium transition. Both express sulphated glycosaminoglycans (GAGs) which are strikingly upregulated during nephron differentiation. However, sodium chlorate, an inhibitor of GAG sulphation, and the GAG-degrading enzymes heparitinase plus chondroitinase, did not prevent nephron development. In contrast, ureteric bud growth and branching were reversibly inhibited by the above reagents, the inhibition correlating quantitatively with sulphated GAG deprivation caused by a range of chlorate concentrations. Growth and branching could be independently restored during GAG deprivation by hepatocyte growth factor and phorbol-12-myristate acetate (PMA) respectively. Together these signalling effectors stimulated both branch initiation and growth. Thus growth and morphogenesis of ureteric bud involve distinct signalling pathways both regulated by GAGs.
Davies
J
J
Cancer Research Campaign Epithelial Morphogenesis Research Group, School of Biological Sciences, University of Manchester, UK.
Lyon
M
M
Gallagher
J
J
Garrod
D
D
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation; D002704:Chlorates / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000196:embryology*; D051379:Mice; D008815:Mice, Inbred Strains; D009024:Morphogenesis / Q000187:drug effects; D009924:Organ Culture Techniques; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014513:Ureter / Q000187:drug effects / Q000196:embryology*
D002704:Chlorates; D006025:Glycosaminoglycans; D003994:Bucladesine; D017228:Hepatocyte Growth Factor; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase; D013755:Tetradecanoylphorbol Acetate; C032706:sodium chlorate