Bone morphogenetic proteins (BMPs) are multifunctional growth factors originally identified by their ability to induce ectopic bone formation. To investigate the function of one of the BMPs, BMP-7, we have generated BMP-7-deficient mice using embryonic stem cell technology. BMP-7-deficient mice die shortly after birth because of poor kidney development. Histological analysis of mutant embryos at several stages of development revealed that metanephric mesenchymal cells fail to differentiate, resulting in a virtual absence of glomerulus in newborn kidneys. In situ hybridization analysis showed that the absence of BMP-7 affects the expression of molecular markers of nephrogenesis, such as Pax-2 and Wnt-4 between 12.5 and 14.5 days postcoitum (dpc). This identifies BMP-7 as an inducer of nephrogenesis. In addition, BMP-7-deficient mice have eye defects that appear to originate during lens induction. Finally, BMP-7-deficient mice also have skeletal patterning defects restricted to the rib cage, the skull, and the hindlimbs.
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Bone morphogenetic protein-7 (osteogenic protein-1, OP-1) and tooth development.
J Dent Res
April 1998
Department of Oral Cell Biology, ACTA, Vrije Universiteit, Amsterdam, The Netherlands.
Bone morphogenetic proteins (BMPs) form a family of growth factors originally isolated from extracellular bone matrix that are capable of inducing bone formation ectopically. We studied the expression, tissue localization, and function of BMP-7 (OP-1) during tooth development in rodents. Patterns of BMP-7 gene expression and peptide distribution indicated that BMP-7 was present in dental epithelium during the dental lamina, bud, and cap stages.
View Article and Find Full Text PDFBMP 7 is required for nephrogenesis, eye development, and skeletal patterning.
Ann N Y Acad Sci
June 1996
Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
In summary, the generation of BMP-7-deficient mice has provided additional evidence that this family of growth factors regulate many morphogenetic processes including but not limited to skeletal development. In particular our experiments demonstrate that BMP 7 acts as an early inducer of glomeruli formation, and that it is required for skeletal patterning and lens formation. Our results not only demonstrate that BMP 7 is involved in the differentiation of several organs during development, but also raise the hypothesis that mutations in the Bmp 7 gene itself or in the genetic pathway could be responsible for several human genetic diseases in which glomerulus formation is impaired.
View Article and Find Full Text PDFAnalysis of limb patterning in BMP-7-deficient mice.
Dev Genet
February 1997
GSF, Forschungszentrum für Umwelt und Gesundheit, Institut für Säugetiergenetik, Neuherberg, Oberschleissheim-Munich, Germany.
Bone morphogenetic proteins (BMPs) are polypeptide signaling molecules, belonging to the TGF-beta superfamily. They were originally identified by their ability to induce ectopic bone formation, but their expression patterns in embryos suggest multiple functions. BMP-7-deficient mice show among other mesodermal and skeletal patterning defects, polydactyly in the hindlimbs [Luo G, Hofmann C, Bronckers ALJJ, Sohocki M, Bradley A, Karsenty G (1995): Genes Dev 9:2808-2820; Dudley AT, Lyons KM, Robertson EJ (1995): Genes Dev 9:2795-2807].
View Article and Find Full Text PDFBMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning.
Genes Dev
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Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Bone morphogenetic proteins (BMPs) are multifunctional growth factors originally identified by their ability to induce ectopic bone formation. To investigate the function of one of the BMPs, BMP-7, we have generated BMP-7-deficient mice using embryonic stem cell technology. BMP-7-deficient mice die shortly after birth because of poor kidney development.
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