Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme
Todd D. Camenisch,Andrew P. Spicer,Andrew P. Spicer,Tammy Brehm-Gibson,Jennifer Biesterfeldt,Mary Lou Augustine,Anthony Calabro,Steven W. Kubalak,Scott E. Klewer,John A. McDonald +9 more
TLDR
The results demonstrate the importance of HA in mammalian embryogenesis and the pivotal role of Has2 during mammalian development and reveal a previously unrecognized pathway for cell migration and invasion that is HA-dependent and involves Ras activation.Abstract:
We identified hyaluronan synthase-2 (Has2) as a likely source of hyaluronan (HA) during embryonic development, and we used gene targeting to study its function in vivo. Has2(-/-) embryos lack HA, exhibit severe cardiac and vascular abnormalities, and die during midgestation (E9.5-10). Heart explants from Has2(-/-) embryos lack the characteristic transformation of cardiac endothelial cells into mesenchyme, an essential developmental event that depends on receptor-mediated intracellular signaling. This defect is reproduced by expression of a dominant-negative Ras in wild-type heart explants, and is reversed in Has2(-/-) explants by gene rescue, by administering exogenous HA, or by expressing activated Ras. Conversely, transformation in Has2(-/-) explants mediated by exogenous HA is inhibited by dominant-negative Ras. Collectively, our results demonstrate the importance of HA in mammalian embryogenesis and the pivotal role of Has2 during mammalian development. They also reveal a previously unrecognized pathway for cell migration and invasion that is HA-dependent and involves Ras activation.read more
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CD44: From adhesion molecules to signalling regulators
TL;DR: Cell-adhesion molecules, once believed to function primarily in tethering cells to extracellular ligands, are now recognized as having broader functions in cellular signalling cascades and the CD44 transmembrane glycoprotein family adds new aspects to these roles by participating in signal-transduction processes.
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Hyaluronan: from extracellular glue to pericellular cue
TL;DR: This work highlights a key role for interactions between hyaluronan and tumour cells in several aspects of malignancy and indicates the possibility of new therapeutic strategies.
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Regulation of lung injury and repair by Toll-like receptors and hyaluronan.
Dianhua Jiang,Jiurong Liang,Juan Fan,Shuang Yu,Suping Chen,Yi Luo,Glenn D. Prestwich,Marcella M. Mascarenhas,Hari G. Garg,Deborah A. Quinn,Robert J. Homer,Daniel R. Goldstein,Richard Bucala,Patty J. Lee,Ruslan Medzhitov,Paul W. Noble +15 more
TL;DR: It is reported that hyaluronan degradation products require MyD88 and both Toll-like receptor (TLR)4 and TLR2 in vitro and in vivo to initiate inflammatory responses in acute lung injury and epithelial cell apoptosis after lung injury.
Journal ArticleDOI
The extracellular matrix in development and morphogenesis: a dynamic view.
TL;DR: The importance of ECM as a dynamic repository for growth factors is highlighted along with more recent studies implicating the 3-dimensional organization and physical properties of theECM as it relates to cell signaling and the regulation of morphogenetic cell behaviors.
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Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo.
Yaz Y. Kisanuki,Robert E. Hammer,Jun-ichi Miyazaki,S. Clay Williams,James A. Richardson,Masashi Yanagisawa +5 more
TL;DR: Tie2-Cre transgenic mice are a new genetic tool for the analyses of endothelial cell-lineage and endothelialcell-specific gene targeting and lacZ staining in Tie2- Cre;CAG-CAT-Z embryos is consistent with endocardial-mesenchymal transformation in the atrioventricular canal and outflow tract regions.
References
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LYVE-1, a New Homologue of the CD44 Glycoprotein, Is a Lymph-specific Receptor for Hyaluronan
Suneale Banerji,Jian Ni,Shu-Xia Wang,Steven Clasper,Jeffrey Su,Raija Tammi,Margaret Jones,David A. Jackson +7 more
TL;DR: LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.
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Multiple essential functions of neuregulin in development
Dirk Meyer,Carmen Birchmeier +1 more
TL;DR: It is shown that neUREgulin -/ - embryos die during embryogenesis and display heart malformations, and the phenotype demonstrates that in vivo neuregulin acts locally and frequently in a paracrine manner.
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Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor.
Martin Gassmann,Franca Casagranda,Donata Orioli,Horst H. Simon,Cary Lai,Rüdiger Klein,Greg Lemke +6 more
TL;DR: It is demonstrated that ErbB4 is an essential in vivo regulator of both cardiac muscle differentiation and axon guidance in the central nervous system (CNS) and differences in the hindbrain phenotypes of these mutants are consistent with the action of a new Erb B4 ligand in the CNS.
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Three Isoforms of Mammalian Hyaluronan Synthases Have Distinct Enzymatic Properties
Naoki Itano,Takahiro Sawai,Mamoru Yoshida,Petros Lenas,Yoichi Yamada,Michiko Imagawa,T Shinomura,Michinari Hamaguchi,Yuko Yoshida,Youji Ohnuki,Satoshi Miyauchi,Andrew P. Spicer,John A. McDonald,Koji Kimata +13 more
TL;DR: Comparisons of hyaluronan secreted into the culture media by stable HAS transfectants showed that HAS1 and HAS3 generated hyAluronan with broad size distributions, whereas HAS2 generated hyalons with a broad but extremely large size, which may provide the cells with flexibility in the control of hy aluronan biosynthesis and functions.
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Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis.
TL;DR: The presence of transforming growth factor beta 1 (TGF-beta 1), a potent profibrotic cytokine, in the foci containing activated fibroblasts suggests that matrix-associated TGF- beta 1 may serve as a stimulus for the persistent expression of connective tissue genes.