We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Evidence that bone morphogenetic protein 4 has multiple biological functions during kidney and urinary tract development.
- Authors
Miyazaki, Yoichi; Oshima, Keisuke; Fogo, Agnes; Ichikawa, Iekuni
- Abstract
Evidence that bone morphogenetic protein 4 has multiple biological functions during kidney and urinary tract development. Background. We have suggested that bone morphogenetic protein 4 (BMP4), acting on the Wolffian duct and ureter epithelium, determines the budding site of the ureter by locally antagonizing ubiquitous inductive signal(s) from the metanephric mesenchyme. In the present study, we examine the effect of BMP4 on the development of metanephric and periureteral mesenchymal cells, which express the BMP type I receptor gene, Bmpr1a (Alk3 ). Methods. Urogenital tissues obtained from Bmp4 heterozygous null mutant (Bmp4 +/-) embryos at different stages, and metanephric and ureteral tissue explants cultured in the presence of recombinant BMP4 were subjected to morphologic, immunohistochemical and in situ hybridization analyses. To examine the chemotactic activity of BMP4 for periureteral mesenchymal cells, a modified Boyden chamber assay was performed. Results. Many of the kidneys of newborn Bmp4 +/- mice contained multicystic dysplastic regions. This morphology was preceded by abnormally high apoptotic activity in the metanephric mesenchyme of mutant embryos at E14.5. In whole metanephric explants, BMP4 uniformly promoted the expansion of the Pax2 -negative and weakly Foxd1 (previously Bf2 ) -positive peripheral stromal compartment of metanephric mesenchyme in the presence of fibroblast growth factor 2 (FGF2). In addition, in isolated metanephric mesenchyme, BMP4-loaded beads prevented apoptosis locally. Thus, BMP4 prevents cell death and promotes the growth of the metanephric mesenchyme. The effect of BMP4 on periureteral mesenchyme is different from its effect on metanephric mesenchyme. In utero, periureteral mesenchymal cells condense around the ureter epithelium, followed by differentiation into smooth muscle cells at a site where Bmp4 is intensely expressed. Analysis of Bmp4 +/- ureters at E15.5 reveals that the α-smooth muscle actin...
- Subjects
BONE morphogenetic proteins; MESENCHYME; KIDNEYS
- Publication
Kidney International, 2003, Vol 63, Issue 3, p835
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2003.00834.x