Fibroblast growth factor-10 signals development of von Brunn's nests in the exstrophic bladder.
von Brunn's nests have long been recognized as precursors of benign lesions of the urinary bladder mucosa. We report here that von Brunn's nests are especially prevalent in the exstrophic bladder, a birth defect that predisposes the patient to formation of bladder cancer. Cells of von Brunn's nest were found to coalesce into a stratified, polarized epithelium which surrounds itself with a capsule-like structure rich in types I, III, and IV collagen. Histocytochemical analysis and keratin profiling demonstrated that nested cells exhibited a phenotype similar, but not identical, to that of urothelial cells of transitional epithelium. Immunostaining and in situ hybridization analysis of exstrophic tissue demonstrated that the FGF-10 receptor is synthesized and retained by cells of von Brunn's nest. In contrast, FGF-10 is synthesized and secreted by mesenchymal fibroblasts via a paracrine pathway that targets basal epithelial cells of von Brunn's nests. Small clusters of 10pRp cells, positive for both FGF-10 and its receptor, were observed both proximal to and inside blood vessels in the lamina propria. The collective evidence points to a mechanism where von Brunn's nests develop under the control of the FGF-10 signal transduction system and suggests that 10pRp cells may be the original source of nested cells.
Eastman
Rocky
R
Program in Human Urothelial Biology, Center for Tissue and Cell Sciences, Seattle Children's Research Institute, 1900 9th Ave., Mailstop C9S-5, Seattle, WA 98101, USA.
Leaf
Elizabeth M
EM
Zhang
Dianzhong
D
True
Lawrence D
LD
Sweet
Robert M
RM
Seidel
Kristy
K
Siebert
Joseph R
JR
Grady
Richard
R
Mitchell
Michael E
ME
Bassuk
James A
JA
D000818:Animals; D001746:Bladder Exstrophy / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery; D002454:Cell Differentiation / Q000502:physiology; D003124:Colorimetry; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051523:Fibroblast Growth Factor 7 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D007231:Infant, Newborn; D007633:Keratins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000473:pathology; D016612:Paraffin Embedding; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D019459:Urothelium / Q000166:cytology / Q000502:physiology
C496463:FGF10 protein, human; C496464:Fgf10 protein, mouse; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D007633:Keratins