scholarly journals Inhibition of laminin alpha 1-chain expression leads to alteration of basement membrane assembly and cell differentiation.

1996 ◽  
Vol 133 (2) ◽  
pp. 417-430 ◽  
Author(s):  
A De Arcangelis ◽  
P Neuville ◽  
R Boukamel ◽  
O Lefebvre ◽  
M Kedinger ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Basement Membrane ◽  
Regulatory Element ◽  
Digestive Enzyme ◽  
Eukaryotic Expression ◽  
Basement Membranes ◽  
Chain Gene ◽  
Membrane Assembly ◽  
Development And Differentiation ◽  
Laminin 1

The expression of the constituent alpha 1 chain of laminin-1, a major component of basement membranes, is markedly regulated during development and differentiation. We have designed an antisense RNA strategy to analyze the direct involvement of the alpha 1 chain in laminin assembly, basement membrane formation, and cell differentiation. We report that the absence of alpha 1-chain expression, resulting from the stable transfection of the human colonic cancer Caco2 cells with an eukaryotic expression vector comprising a cDNA fragment of the alpha 1 chain inserted in an antisense orientation, led to (a) an incorrect secretion of the two other constituent chains of laminin-1, the beta 1/gamma 1 chains, (b) the lack of basement membrane assembly when Caco2-deficient cells were cultured on top of fibroblasts, assessed by the absence of collagen IV and nidogen deposition, and (c) changes in the structural polarity of cells accompanied by the inhibition of an apical digestive enzyme, sucrase-isomaltase. The results demonstrate that the alpha 1 chain is required for secretion of laminin-1 and for the assembly of basement membrane network. Furthermore, expression of the laminin alpha 1-chain gene may be a regulatory element in determining cell differentiation.

scholarly journals Sonic hedgehog-dependent synthesis of laminin  1 controls basement membrane assembly in the myotome

Development ◽  
2009 ◽  
Vol 136 (20) ◽  
pp. 3495-3504 ◽  
Author(s):  
C. Anderson ◽  
S. Thorsteinsdottir ◽  
A.-G. Borycki
Keyword(s):  
Basement Membrane ◽  
Sonic Hedgehog ◽  
Membrane Assembly ◽  
Laminin 1

"BM180": a novel basement membrane protein with a role in stimulus-secretion coupling by lacrimal acinar cells

1996 ◽  
Vol 270 (6) ◽  
pp. C1743-C1750 ◽  
Author(s):  
G. W. Laurie ◽  
J. D. Glass ◽  
R. A. Ogle ◽  
C. M. Stone ◽  
J. R. Sluss ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Membrane Protein ◽  
Acinar Cells ◽  
Basement Membranes ◽  
Enzyme Linked Immunosorbent Assay ◽  
Regulated Secretion ◽  
Basement Membrane Protein ◽  
Stimulus Secretion Coupling ◽  
Lacrimal Acinar Cells ◽  
Laminin 1

Regulated secretion requires the developmental coupling of neuronal or hormonal stimuli to an exocytotic response, a multistep pathway whose appearance may be linked with cellular adhesion to the newly formed exocrine cell basement membrane. We screened for adhesion-associated coupling activity using lacrimal acinar cells and have identified “BM180”, a novel basement membrane protein enriched in guanidine HCl extracts of lacrimal and parotid exocrine secretory glands. BM180 resides primarily in a previously inexamined lower molecular-mass basement membrane peak (peak 2) that contains cell adhesion activity inhibitable with the anti-BM180 monoclonal antibody 3E12. Removal of peak 2 by gel filtration or preincubation of basement membrane with 3E12 decreased regulated peroxidase secretion by one-half without affecting constitutive secretion or the amount of cellular peroxidase available for release. Adding back peak 2 restored regulated secretion in a dose-dependent and 3E12-inhibitable manner and suggested a synergistic relationship between BM180 and laminin 1. BM180 has a mobility of 180 and 60 kDa in the absence or presence of dithiothreitol, respectively, and shows no immunological identity by competitive enzyme-linked immunosorbent assay with laminin 1, collagen IV, entactin, fibronectin, BM-40, perlecan, or vitronectin. We propose that BM180 is an important resident of certain glandular basement membranes where it interacts with the cell surface, thereby possibly signaling the appearance of a transducing element in the stimulus-secretion coupling pathway.

Zebrafish mutants identify an essential role for laminins in notochord formation

Development ◽  
2002 ◽  
Vol 129 (13) ◽  
pp. 3137-3146 ◽  
Author(s):  
Michael J. Parsons ◽  
Steven M. Pollard ◽  
Leonor Saúde ◽  
Benjamin Feldman ◽  
Pedro Coutinho ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Positional Cloning ◽  
Essential Role ◽  
Basement Membranes ◽  
Form Complex ◽  
Organ Formation ◽  
Notochord Cells ◽  
Laminin 1

Basement membranes are thought to be essential for organ formation, providing the scaffold on which individual cells organize to form complex tissues. Laminins are integral components of basement membranes. To understand the development of a simple vertebrate organ, we have used positional cloning to characterize grumpy and sleepy, two zebrafish loci known to control notochord formation, and find that they encode laminin β1 and laminin γ1, respectively. Removal of either chain results in the dramatic loss of laminin 1 staining throughout the embryo and prevents formation of the basement membrane surrounding the notochord. Notochord cells fail to differentiate and many die by apoptosis. By transplantation, we demonstrate that, for both grumpy and sleepy, notochord differentiation can be rescued by exogenous sources of the missing laminin chain, although notochordal sources are also sufficient for rescue. These results demonstrate a clear in vivo requirement for laminin β1 and laminin γ1 in the formation of a specific vertebrate organ and show that laminin or the laminin-dependent basement membrane is essential for the differentiation of chordamesoderm to notochord.

Expression of laminin isoforms in mouse myogenic cells in vitro and in vivo

1995 ◽  
Vol 108 (12) ◽  
pp. 3795-3805 ◽  
Author(s):  
F. Schuler ◽  
L.M. Sorokin
Keyword(s):  
In Situ Hybridization ◽  
Basement Membranes ◽  
Chain Gene ◽  
Muscle Fibres ◽  
Myogenic Cells ◽  
Mouse Tissues ◽  
Laminin 1

The expression of laminin-1 (previously EHS laminin) and laminin-2 (previously merosin) isoforms by myogenic cells was examined in vitro and in vivo. No laminin alpha 2 chainspecific antibodies react with mouse tissues, 50 rat monoclonal antibodies were raised against the mouse laminin alpha 2 chain: their characterization is described here. Myoblasts and myotubes from myogenic cell lines and primary myogenic cultures express laminin beta 1 and gamma 1 chains and form a complex with a 380 kDa alpha chain identified as laminin alpha 2 by immunofluorescence, immunoprecipitation and PCR. PCR from C2C12 myoblasts and myotubes for the laminin alpha 2 chain gene (LamA2) provided cDNA sequences which were used to investigate the in vivo expression of mouse LamA2 mRNA in embryonic tissues by in situ hybridization. Comparisons were made with specific probes for the laminin alpha 1 chain gene (LamA1). LamA2 but not LamA1 mRNA was expressed in myogenic tissues of 14- and 17-day-old mouse embryos, while the laminin alpha 2 polypeptide was localized in adjacent basement membranes in the muscle fibres. In situ hybridization also revealed strong expression of the LamA2 mRNA in the dermis, indicating that laminin alpha 2 is expressed other than by myogenic cells in vivo. Immunofluorescence studies localized laminin alpha 2 in basement membranes of basal keratinocytes and the epithelial cells of hair follicles, providing new insight into basement membrane assembly during embryogenesis. In vitro cell attachment assays revealed that C2C12 and primary myoblasts adhere to laminin-1 and -2 isoforms in a similar manner except that myoblast spreading was significantly faster on laminin-2. Taken together, the data suggest that laminins 1 and 2 play distinct roles in myogenesis.

scholarly journals Laminin  1 globular domains 4-5 induce fetal development but are not vital for embryonic basement membrane assembly

2005 ◽  
Vol 102 (5) ◽  
pp. 1502-1506 ◽  
Author(s):  
S. Scheele ◽  
M. Falk ◽  
A. Franzen ◽  
F. Ellin ◽  
M. Ferletta ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Fetal Development ◽  
Membrane Assembly ◽  
Laminin 1

scholarly journals Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome–associated proteins

2012 ◽  
Vol 197 (5) ◽  
pp. 677-689 ◽  
Author(s):  
Daiji Kiyozumi ◽  
Makiko Takeichi ◽  
Itsuko Nakano ◽  
Yuya Sato ◽  
Tomohiko Fukuda ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Direct Consequence ◽  
Basement Membranes ◽  
Dystrophic Epidermolysis Bullosa ◽  
Membrane Assembly ◽  
Fraser Syndrome ◽  
Basement Membrane Protein ◽  
Integrin Binding Site ◽  
Associated Proteins

Dysfunction of the basement membrane protein QBRICK provokes Fraser syndrome, which results in renal dysmorphogenesis, cryptophthalmos, syndactyly, and dystrophic epidermolysis bullosa through unknown mechanisms. Here, we show that integrin α8β1 binding to basement membranes was significantly impaired in Qbrick-null mice. This impaired integrin α8β1 binding was not a direct consequence of the loss of QBRICK, which itself is a ligand of integrin α8β1, because knock-in mice with a mutation in the integrin-binding site of QBRICK developed normally and do not exhibit any defects in integrin α8β1 binding. Instead, the loss of QBRICK significantly diminished the expression of nephronectin, an integrin α8β1 ligand necessary for renal development. In vivo, nephronectin associated with QBRICK and localized at the sublamina densa region, where QBRICK was also located. Collectively, these findings indicate that QBRICK facilitates the integrin α8β1–dependent interactions of cells with basement membranes by regulating the basement membrane assembly of nephronectin and explain why renal defects occur in Fraser syndrome.

scholarly journals Laminin

2004 ◽  
Vol 164 (7) ◽  
pp. 959-963 ◽  
Author(s):  
Takako Sasaki ◽  
Reinhard Fässler ◽  
Erhard Hohenester
Keyword(s):  
Basement Membrane ◽  
Membrane Assembly ◽  
Structural Methods ◽  
Laminin 1

Laminin-1 is emerging as the key molecule in early embryonic basement membrane assembly. Here we review recent insights into its functions gained from the synergistic application of genetic and structural methods.

Altered synthesis of laminin 1 and absence of basement membrane component deposition in (beta)1 integrin-deficient embryoid bodies

2000 ◽  
Vol 113 (2) ◽  
pp. 259-268 ◽  
Author(s):  
M. Aumailley ◽  
M. Pesch ◽  
L. Tunggal ◽  
F. Gaill ◽  
R. Fassler
Keyword(s):  
Basement Membrane ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Mouse Genetics ◽  
Embryoid Bodies ◽  
Membrane Formation ◽  
Beta 1 Integrin ◽  
Laminin 1

Basement membranes are the earliest extracellular matrices produced during embryogenesis. They result from synthesis and assembly into a defined supramolecular architecture of several components, including laminins, collagen IV, nidogen, and proteoglycans. In vitro studies have allowed us to propose an assembly model based on the polymerisation of laminin and collagen IV in two separate networks associated together by nidogen. How nucleation of polymers and insolubilisation of the different components into a basement membrane proceed in vivo is, however, unknown. A most important property of several basement membrane components is to provide signals controling the activity of adjacent cells. The transfer of information is mediated by interactions with cell surface receptors, among them integrins. Mouse genetics has demonstrated that the absence of these interactions is not compatible with development as deletion of either laminin (gamma)1 chain or integrin (beta)1 chain lead to lethality of mouse embryos at the peri-implantation stage. We have used embyoid bodies as a model system recapitulating the early steps of embryogenesis to unravel the respective roles of laminin and (beta)1 integrins in basement membrane formation. Our data show that there is formation of a basal lamina in wild-type, but not in (beta)1-integrin deficient, embryoid bodies. Surprisingly, in the absence of (beta)1 integrins, laminin 1 was not secreted in the extracellular space due to a rapid switch off of laminin (alpha)1 chain synthesis which normally drives the secretion of laminin heterotrimers. These results indicate that (beta)1 integrins are required for the initiation of basement membrane formation, presumably by applying a feed-back regulation on the expression of laminin (alpha)1 chain and other components of basement membranes.

Deficiency of β1 Integrins in Teratoma Interferes with Basement Membrane Assembly and Laminin-1 Expression

1998 ◽  
Vol 238 (1) ◽  
pp. 70-81 ◽  
Author(s):  
Takako Sasaki ◽  
Erik Forsberg ◽  
Wilhelm Bloch ◽  
Klaus Addicks ◽  
Reinhard Fässler ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Membrane Assembly ◽  
Β1 Integrins ◽  
Laminin 1

scholarly journals Non-muscle alpha-dystroglycan is involved in epithelial development.

1995 ◽  
Vol 130 (1) ◽  
pp. 79-91 ◽  
Author(s):  
M Durbeej ◽  
E Larsson ◽  
O Ibraghimov-Beskrovnaya ◽  
S L Roberds ◽  
K P Campbell ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Kidney Development ◽  
Physiological Role ◽  
Epithelial Differentiation ◽  
Basement Membranes ◽  
Metanephric Mesenchyme ◽  
Mouse Development ◽  
Alpha Dystroglycan ◽  
Laminin 1

The dystroglycan complex is a transmembrane linkage between the cytoskeleton and the basement membrane in muscle. One of the components of the complex, alpha-dystroglycan binds both laminin of muscle (laminin-2) and agrin of muscle basement membranes. Dystroglycan has been detected in nonmuscle tissues as well, but the physiological role in nonmuscle tissues has remained unknown. Here we show that dystroglycan during mouse development in nonmuscle tissues is expressed in epithelium. In situ hybridization revealed strong expression of dystroglycan mRNA in all studied epithelial sheets, but not in endothelium or mesenchyme. Conversion of mesenchyme to epithelium occurs during kidney development, and the embryonic kidney was used to study the role of alpha-dystroglycan for epithelial differentiation. During in vitro culture of the metanephric mesenchyme, the first morphological signs of epithelial differentiation can be seen on day two. Northern blots revealed a clear increase in dystroglycan mRNA on day two of in vitro development. A similar increase of expression on day two was previously shown for laminin alpha 1 chain. Immunofluorescence showed that dystroglycan is strictly located on the basal side of developing kidney epithelial cells. Monoclonal antibodies known to block binding of alpha-dystroglycan to laminin-1 perturbed development of epithelium in kidney organ culture, whereas control antibodies did not do so. We suggest that the dystroglycan complex acts as a receptor for basement membrane components during epithelial morphogenesis. It is likely that this involves binding of alpha-dystroglycan to E3 fragment of laminin-1.

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