The Experts below are selected from a list of 2373 Experts worldwide ranked by ideXlab platform
José M. De Jesús-escobar - One of the best experts on this subject based on the ideXlab platform.
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Ectopic Noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear.
Developmental Biology, 1999Co-Authors: Weise Chang, Fábio Daumas Nunes, José M. De Jesús-escobarAbstract:Bone morphogenetic Protein 4 (Bmp4) is expressed during multiple stages of development of the chicken inner ear. At the otocyst stage, Bmp4 is expressed in each presumptive sensory organ, as well as in the mesenchymal cells surrounding the region of the otocyst that is destined to form the semicircular canals. After the formation of the gross anatomy of the inner ear, Bmp4 expression persists in some sensory organs and restricted domains of the semicircular canals. To address the role of this gene in inner ear development, we blocked BMP4 function(s) by delivering one of its antagonists, Noggin, to the developing inner ear in ovo. Exogenous Noggin was delivered to the developing otocyst by using a replication-competent avian retrovirus encoding the Noggin cDNA (RCAS-N) or implanting beads coated with Noggin Protein. Noggin treatment resulted in a variety of phenotypes involving both sensory and nonsensory components of the inner ear. Among the nonsensory structures, the semicircular canals were the most sensitive and the endolymphatic duct and sac most resistant to exogenous Noggin. Noggin affected the proliferation of the primordial canal outpouch, as well as the continual outgrowth of the canal after its formation. In addition, Noggin affected the structural patterning of the cristae, possibly via a decrease of Msx1 and p75NGFR expression. These results suggest that BMP4 and possibly other BMPs are required for multiple phases of inner ear development.
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The Spemann organizer signal Noggin binds and inactivates bone morphogenetic Protein 4
Cell, 1996Co-Authors: Lyle B Zimmerman, José M. De Jesús-escobarAbstract:Signals released by the Spemann organizer of the amphibian gastrula can directly induce neural tissue from ectoderm and can dorsalize ventral mesoderm to form muscle. The secreted polypeptide Noggin mimics these activities and is expressed at the appropriate time and place to participate in the organizer signal. Neural induction and mesoderm dorsalization are antagonized by bone morphogenetic Proteins (BMPs), which induce epidermis and ventral mesoderm instead. Here we report that Noggin Protein binds BMP4 with high affinity and can abolish BMP4 activity by blocking binding to cognate cell-surface receptors. These data suggest that Noggin secreted by the organizer patterns the embryo by interrupting BMP signaling.
Dale Frank - One of the best experts on this subject based on the ideXlab platform.
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competition between Noggin and bone morphogenetic Protein 4 activities may regulate dorsalization during xenopus development
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: Yael Reemkalma, Teresa M Lamb, Dale FrankAbstract:Abstract Bone morphogenetic Protein 4 (BMP-4) induces ventral mesoderm but represses dorsal mesoderm formation in Xenopus embryos. We show that BMP-4 inhibits two signaling pathways regulating dorsal mesoderm formation, the induction of dorsal mesoderm (Spemann organizer) and the dorsalization of ventral mesoderm. Ectopic expression of BMP-4 RNA reduces goosecoid and forkhead-1 transcription in whole embryos and in activin-treated animal cap explants. Embryos and animal caps overexpressing BMP-4 transcribe high levels of genes expressed in ventral mesoderm (Xbra, Xwnt-8, Xpo, Mix.1, XMyoD). The Spemann organizer is ventralized in these embryos; abnormally high levels of Xwnt-8 mRNA and low levels of goosecoid mRNA are detected in the organizer. In addition, the organizer loses the ability to dorsalize neighboring ventral marginal zone to muscle. Overexpression of BMP-4 in ventral mesoderm inhibits its response to dorsalization signals. Ventral marginal zone explants ectopically expressing BMP-4 form less muscle when treated with soluble Noggin Protein or when juxtaposed to a normal Spemann organizer in comparison to control explants. Endogenous BMP-4 transcripts are downregulated in ventral marginal zone explants dorsalized by Noggin, in contrast to untreated explants. Thus, while BMP-4 inhibits Noggin Protein activity, Noggin downregulates BMP-4 expression by dorsalizing ventral marginal zone to muscle. Noggin and BMP-4 activities may control the lateral extent of dorsalization within the marginal zone. Competition between these two molecules may determine the final degree of muscle formation in the marginal zone, thus defining the border between dorsolateral and ventral mesoderm.
Hari A Reddi - One of the best experts on this subject based on the ideXlab platform.
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bone morphogenetic Protein bmp 6 signaling and bmp antagonist Noggin in prostate cancer
Cancer Research, 2004Co-Authors: Dominik R Haudenschild, Sabrina M Palmer, Timothy A Moseley, Zongbing You, Hari A ReddiAbstract:It has been proposed that the osteoblastic nature of prostate cancer skeletal metastases is due in part to elevated activity of bone morphogenetic Proteins (BMPs). BMPs are osteoinductive morphogens, and elevated expression of BMP-6 correlates with skeletal metastases of prostate cancer. In this study, we investigated the expression levels of BMPs and their modulators in prostate, using microarray analysis of cell cultures and gene expression. Addition of exogenous BMP-6 to DU-145 prostate cancer cell cultures inhibited their growth by up-regulation of several cyclin-dependent kinase inhibitors such as p21/CIP, p18, and p19. Expression of Noggin, a BMP antagonist, was significantly up-regulated by BMP-6 by microarray analysis and was confirmed by quantitative reverse transcription-polymerase chain reaction and at the Protein level. Noggin Protein was present in prostate biopsies and localized to the epithelial components of prostate by immunohistochemistry. Recombinant Noggin inhibited the function of BMP-6, suggesting a negative feedback regulation of BMP activity and indicating a strategy for the development of a novel therapeutic target in the treatment of painful osteosclerotic bone metastases of prostate cancer.
Xintao Shuai - One of the best experts on this subject based on the ideXlab platform.
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ph sensitive nanocarrier mediated codelivery of simvastatin and Noggin sirna for synergistic enhancement of osteogenesis
ACS Applied Materials & Interfaces, 2018Co-Authors: Jinsheng Huang, Chaowen Lin, Jintao Fang, Jin Wang, S Z Deng, Sheng Zhang, Xiaoreng Feng, Bin Chen, Du Cheng, Xintao ShuaiAbstract:The inexpensive hypolipidemic drug simvastatin (SIM), which promotes bone regeneration by enhancing bone morphogenetic Protein 2 (BMP-2) expression, has been regarded as an ideal alternative to BMP-2 therapy. However, SIM has low bioavailability and may induce the upregulation of the BMP-2-antagonistic Noggin Protein, which greatly limits the osteogenic effect. Here, a pH-sensitive copolymer, monomethoxy-poly(ethylene glycol)- b-branched polyethyleneimine- b-poly( N-( N', N'-diisopropylaminoethyl)- co-benzylamino)aspartamide (mPEG-bPEI-PAsp(DIP-BzA)) (PBP), was synthesized and self-assembled into a cationic micelle. SIM and siRNA targeting the Noggin gene (N-siRNA) were loaded into the PAsp(DIP-BzA) core and the cationic bPEI interlayer of the micelle via hydrophobic and electrostatic interactions, respectively. The SIM-loaded micelle effectively delivered SIM into preosteoblast MC3T3-E1 cells and rapidly released it inside the acidic lysosome, resulting in the elevated expression of BMP-2. Meanwhile, the codelivered N-siRNA effectively suppressed the expression of Noggin. Consequently, SIM and N-siRNA synergistically increased the BMP-2/Noggin ratio and resulted in an obviously higher osteogenetic effect than did simvastatin or N-siRNA alone, both in vitro and in vivo.
Lyle B Zimmerman - One of the best experts on this subject based on the ideXlab platform.
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The Spemann organizer signal Noggin binds and inactivates bone morphogenetic Protein 4
Cell, 1996Co-Authors: Lyle B Zimmerman, José M. De Jesús-escobarAbstract:Signals released by the Spemann organizer of the amphibian gastrula can directly induce neural tissue from ectoderm and can dorsalize ventral mesoderm to form muscle. The secreted polypeptide Noggin mimics these activities and is expressed at the appropriate time and place to participate in the organizer signal. Neural induction and mesoderm dorsalization are antagonized by bone morphogenetic Proteins (BMPs), which induce epidermis and ventral mesoderm instead. Here we report that Noggin Protein binds BMP4 with high affinity and can abolish BMP4 activity by blocking binding to cognate cell-surface receptors. These data suggest that Noggin secreted by the organizer patterns the embryo by interrupting BMP signaling.