Growth and branching morphogenesis of rat collecting duct anlagen in the absence of metanephrogenic mesenchyme.
The growth and differentiation of the epithelium in many tissues is mediated by interactions with the adjacent mesenchyme, but the mechanisms responsible remain undefined. To identify the factors involved in the growth and branching morphogenesis of ureteric bud, which is the collecting duct anlagen, buds from 13-gestation-day rat embryos were separated from the metanephrogenic mesenchyme and explanted to culture dishes coated with gelled type I collagen in a defined medium. Under these conditions buds attached to the substrate and grew out without indication of cell senescence. When buds were instead suspended in gelled type I collagen, branching morphogenesis was observed despite the absence of mesenchyme although it was not as extensive as in vivo. Since growth occurred much more slowly in culture than expected, culture conditions were varied in attempts to accelerate the process. Despite extensive screening of matrices and growth factors, only epidermal and endothelial cell growth factors stimulated growth to a significant extent. Transforming growth factor-beta, on the other hand, was a potent inhibitor of growth. Homogenates from tumors that caricature metanephrogenic mesenchyme were highly mitogenic for bud cells and, thus, will be a source of material for characterizing regulatory factors involved in renal growth. These studies show that growth and branching morphogenesis of the ureteric bud can occur without direct cell-cell interactions with the metanephrogenic mesenchyme and that matrices and factors secreted by the mesenchyme may mediated these activities in vivo.
Perantoni
A O
AO
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702.
Williams
C L
CL
Lewellyn
A L
AL
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003094:Collagen; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D007680:Kidney Neoplasms / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D009024:Morphogenesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D016228:Endothelial Growth Factors; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D003094:Collagen