Adèle Arcangelis | IGBMC - Academia.edu (original) (raw)

Papers by Adèle Arcangelis

Cell Adhesion & Migration, 2013

BMC Neuroscience, 2007

The kelch repeat protein muskelin mediates cytoskeletal responses to the extracellular matrix pro... more The kelch repeat protein muskelin mediates cytoskeletal responses to the extracellular matrix protein thrombospondin 1, (TSP1), that is known to promote synaptogenesis in the central nervous system (CNS). Muskelin displays intracellular localization and affects cytoskeletal organization in adherent cells. Muskelin is expressed in adult brain and has been reported to bind the Cdk5 activator p39, which also facilitates the formation of functional synapses. Since little is known about muskelin in neuronal tissues, we here analysed the tissue distribution of muskelin in rodent brain and analysed its subcellular localization using cultured neurons from multiple life stages.

The expression of the constituent o~1 chain of laminin-1, a major component of basement mem- bran... more The expression of the constituent o~1 chain of laminin-1, a major component of basement mem- branes, is markedly regulated during development and differentiation. We have designed an antisense RNA strategy to analyze the direct involvement of the ~1 chain in laminin assembly, basement membrane forma- tion, and cell differentiation. We report that the ab- sence of otl-chain expression, resulting from

Laminins are expressed highly in blood vessel basement membranes and have been implicated in angi... more Laminins are expressed highly in blood vessel basement membranes and have been implicated in angiogenesis. α6β1-and α6β4-integrins are major receptors for laminins in endothelial cells, but the precise role of endothelial α6-integrin in tumour angiogenesis is not clear. We show that blood vessels in human invasive ductal carcinoma of the breast have decreased expression of the α6-integrin-subunit when compared with normal breast tissue. These data suggest that a decrease in α6-integrin-subunit expression in endothelial cells is associated with tumour angiogenesis. To test whether the loss of the endothelial α6-integrin subunit affects tumour growth and angiogenesis, we generated α6fl/fl-Tie1Cre+ mice and showed that endothelial deletion of α6-integrin is sufficient to enhance tumour size and tumour angiogenesis in both murine B16F0 melanoma and Lewis cell lung carcinoma.

Current Biology, 2002

culaire et Cellulaire of cells to their substrate regulates cell motility and cell shape and is r... more culaire et Cellulaire of cells to their substrate regulates cell motility and cell shape and is required for cell migration or differentiation, CNRS/INSERM/ULP BP 163 tissue organization, and integrity [1, 2]. Integrins are the main receptors that mediate cellular interactions with 67404 Illkirch Communauté urbaine de Strasbourg ECM ligands, such as laminins, collagens, and fibronectin. Genetic analysis has shown that integrins and ECM France 2 Department of Biology molecules are required in vertebrates and invertebrates for many aspects of embryogenesis, particularly for epi-Johns Hopkins University Baltimore, Maryland 21218 thelial (epidermal attachment, lung development, and morphogenesis of the apical ectodermal ridge) and nervous system development (brain lamination, neuroblast migration, and axon fasciculation) [1, 2]. In some in-Summary stances, it has allowed us to define which specific ligands or receptors are required in a given tissue [1, 2]. Background: Integrins are heterodimeric (␣␤) trans-However, while the

Gene Expression Patterns, 2004

Fascin-1 is an actin-bundling protein that contributes to the architecture and function of cell p... more Fascin-1 is an actin-bundling protein that contributes to the architecture and function of cell protrusions and microfilaments in cell adhesion, interactions and motility. Fascin-1 has been studied in cultured cells and by biophysical methods, but little is known about its distribution and functions in vertebrate development. As a first step to understanding the role of fascin-1 in embryogenesis, we have

European Journal of Neuroscience, 2010

During cerebral cortex development, post-mitotic neurons interact with radial glial fibers and th... more During cerebral cortex development, post-mitotic neurons interact with radial glial fibers and the extracellular environment to migrate away from the ventricular region and form a correct laminar structure. Integrin receptors are major mediators of cell-cell and cellextracellular matrix interactions. Several integrin heterodimers are present during formation of the cortical layers. The a5b1 receptor is expressed in the neural progenitors of the ventricular zone during cerebral cortex formation. Using in utero electroporation to introduce short hairpin RNAs in the brain at embryonic day 15.5, we were able to inhibit acutely the expression of a5 integrin in the developing cortex. The knockdown of a5 integrin expression level in neural precursors resulted in an inhibition of radial migration, without perturbing the glial scaffold. Moreover, the same inhibitory effect on neuronal migration was observed after electroporation of a Cre recombinase expression plasmid into the neural progenitors of conditional knockout mice for a5 integrin. In both types of experiments, the electroporated cells expressing reduced levels of a5 integrin accumulated in the premigratory region with an abnormal morphology. At postnatal day 2, ectopic neurons were observed in cortical layer V, while a deficit of neurons was observed in cortical layer II-IV. We show that these neurons do not express a layer V-specific marker, suggesting that they have not undergone premature differentiation. Overall, these results indicate that a5b1 integrin functions in the regulation of neural morphology and migration during cortical development, playing a role in cortical lamination.

International Journal of Oncology, 2014

The α6 integrin subunit (α6) has been implicated in cancer cell migration and in the progression ... more The α6 integrin subunit (α6) has been implicated in cancer cell migration and in the progression of several malignancies, but its role in tumor angiogenesis is unclear. In mice, anti-α6 blocking antibodies reduce tumor angiogenesis, whereas Tie1-dependent α6 gene deletion enhances neovessel formation in melanoma and lung carcinoma. To clarify the discrepancy in these results we used the cre-lox system to generate a mouse line, α6fl/fl-Tie2Cre + , with α6 gene deletion specifically in Tie2-lineage cells: endothelial cells, pericytes, subsets of hematopoietic stem cells, and Tie2-expressing monocytes/macrophages (TEMs), known for their proangiogenic properties. Loss of α6 expression in α6fl/fl-Tie2Cre + mice reduced tumor growth in a murine B16F10 melanoma model. Immunohistological analysis of the tumors showed that Tie2-dependent α6 gene deletion was associated with reduced tumor vascularization and with reduced infiltration of proangiogenic Tie2-expressing macrophages. These findings demonstrate that α6 integrin subunit plays a major role in tumor angiogenesis and TEM infiltration. Targeting α6 could be used as a strategy to reduce tumor growth.

European Journal of Cell Biology, 2011

Hemidesmosomes (HDs) are essential anchorage junctions which mediate the firm attachment of epith... more Hemidesmosomes (HDs) are essential anchorage junctions which mediate the firm attachment of epithelia to the underlying basement membranes, of which one main component is the integrin α6β4. These specific junctions are also able to trigger signalling pathways, via the recruitment and interactions of signalling molecules with HD components such as the cytoplasmic tail of the β4 integrin or the plakin

Trends in Genetics, 2000

The analysis of mutant mice is bringing novel insights on the role of extracellular matrix (ECM) ... more The analysis of mutant mice is bringing novel insights on the role of extracellular matrix (ECM) and integrin receptors during a variety of physiological processes, including embryonic development. The requirement of these adhesion molecules in epithelial morphogenesis or histogenesis in organs such as kidneys and lungs, in limbs, and in the development of mesoderm and the nervous system has been unraveled by the study of single or compound mutants. Their role in tissue integrity has also been highlighted. Models have been produced that should prove very useful in defining the cellular mechanisms and the functions of integrins and ECM signaling cascades in vivo.

The Journal of Cell Biology, 1997

To explore the role of homeobox genes in

The Journal of Cell Biology, 1996

The expression of the constituent o~1 chain of

The International Journal of Biochemistry & Cell Biology, 2007

Muskelin is a member of the kelch-repeat superfamily of proteins, identified as an intracellular ... more Muskelin is a member of the kelch-repeat superfamily of proteins, identified as an intracellular protein involved in cell spreading responses to thombospondin-1. Muskelin is expressed by many adult tissues and has an evolutionarily conserved, multidomain architecture consisting of an amino-terminal discoidin-like domain, a central alpha-helical region and six kelch-repeats that are predicted to form a beta-propeller structure. We previous demonstrated that muskelin molecules undergo head-to-tail association, however the physiological, post-translational regulation of muskelin is not well understood. Here, we have examined the expression of muskelin during mouse embryonic development and report widespread expression that includes muscle tissues, multiple epithelia and the brain. In cultured skeletal myoblasts and vascular smooth muscle cells, muskelin exists as a complex set of isoelectric variants. Five potential sites for phosphorylation by protein kinase C (PKC), are conserved between vertebrate and Drosophila muskelins, therefore we examined the hypothesis that muskelin is regulated post-translationally by PKC activity. We demonstrate that PKC activation or inhibition regulates the profile of endogenous muskelin isoelectric variants and that muskelin is a substrate for PKCalphain vitro. Wild-type GFP-muskelin and a panel of alanine point mutations were used to test the sensitivity of self-association to PKC activation. Mutation of two of the sites, S324 and T515, partially inhibited the ability of muskelin to self-associate in cells and inhibited responsiveness to activated PKC. Interestingly, both sites are predicted to lie in surface-exposed loops on the same side of the beta-propeller, implicating a common binding interface.

International Journal of Cancer, 2001

... Overexpression of laminin α1 chain in colonic cancer cells induces an increase in tumor growt... more ... Overexpression of laminin α1 chain in colonic cancer cells induces an increase in tumor growth. Adèle De Arcangelis 1 ,; Olivier Lefebvre 1 ,; Agnés Méchine-Neuville 2 ,; Christiane Arnold 1 ,;Annick Klein 1 ,; Lionel Rémy 3 ,; Michèle Kedinger 1 ,; Patricia Simon-Assmann 1,*,. ...

Development, 2006

Radial glial cells have been shown to act as neuronal precursors in the developing cortex and to ... more Radial glial cells have been shown to act as neuronal precursors in the developing cortex and to maintain their radial processes attached to the basement membrane (BM) during cell division. Here, we examined a potential role of direct signalling from the BM to radial glial cells in three mouse mutants where radial glia attachment to the BM is disrupted. This is the case if the nidogen-binding site of the laminin gamma1 chain is mutated, in the absence of alpha6 integrin or of perlecan, an essential BM component. Surprisingly, cortical radial glial cells lacking contact to the BM were not affected in their proliferation, interkinetic nuclear migration, orientation of cell division and neurogenesis. Only a small subset of precursors was located ectopically within the cortical parenchyma. Notably, however, neuronal subtype composition was severely disturbed at late developmental stages (E18) in the cortex of the laminin gamma1III4-/- mice. Thus, although BM attachment seems dispensable for precursor cells, an intact BM is required for adequate neuronal composition of the cerebral cortex.

Experientia, 1995

Intestinal morphogenesis and differentiation are dependent on heterotypic cell interactions betwe... more Intestinal morphogenesis and differentiation are dependent on heterotypic cell interactions between embryonic epithelial cells (endoderm) and stromal cells (mesenchyme). Extracellular matrix molecules represent attractive candidates for regulators of these interactions. The structural and functional diversity of the extracellular matrix as intestinal development proceeds is demonstrated by 1) spatio-temporal specific expression of the classically described constituents, 2) the finding of laminin and collagen IV variants, 3) changes in the ratio of individual constituent chains, and 4) a stage-specific regulation of basement membrane molecule production, in particular by glucocorticoids. The orientation/assembly of these extracellular matrix molecules could direct precise cellular functions through interactions via integrin molecules. The involvement of extracellular matrix, and in particular basement membrane molecules in heterotypic cell interactions leading to epithelial cell differentiation, has been highlighted by the use of experimental models such as cocultures, hybrid intestines and antisense approaches. These models allowed us to conclude that a correct elaboration and assembly of the basement membrane, following close contacts between epithelial and fibroblastic cells, is necessary for the expression of differentiation markers such as digestive enzymes.

Cardiovascular Research, 2012

Integrins a6b1 and a6b4 are receptors for laminins, the main components of the basement membrane ... more Integrins a6b1 and a6b4 are receptors for laminins, the main components of the basement membrane underlying the endothelial cells. In vitro, a6 integrin subunit (a6) expression at the surface of endothelial cells and their progenitors (EPCs) is up-regulated by pro-angiogenic growth factors and is crucial for adhesion, migration, and pseudotube formation. We investigated the role for a6 in post-ischaemic vascular repair in vivo.

Journal of Neurocytology, 2005

Integrins are heterodimeric cell surface receptors that mediate developmental events by binding e... more Integrins are heterodimeric cell surface receptors that mediate developmental events by binding extracellular matrix ligands. Several lines of evidence suggest a role for integrins, specifically the α6 subunit, in neuronal migration, neurite outgrowth, and axon guidance during olfactory development. Therefore, we undertook an analysis of the expression of the α6 subunit in the olfactory system of the embryonic and early postnatal mouse to understand the role it may play during neural development. In addition, as a functional assay we examined the developmental effects of the loss of this subunit on olfactory development by analyzing an α6 knockout (α6 − /− ). Immunohistochemical analyses and confocal microscopy were used to examine α6 expression in the CD-1 embryonic and early postnatal olfactory system and also to examine the organization of the olfactory system in the α6 − /− mouse. In CD-1 mice from E13 to E17, α6 localizes in radial patterns extending from the core of the olfactory bulb to the nerve layer and colocalizes with RC2, an antibody specific for radial glia. By the day of birth (P0; ∼ E19), expression is limited to the external plexiform layer and the olfactory nerve layer, where it colocalizes with laminin and p75. In the α6 − /− mouse, areas of ectopic granule cells were observed in the mitral cell layer of the olfactory bulb. These ectopias coincided with areas of disorganization of the radial glial processes and breaks in the mitral cell layer. These observations suggest a role for α6 integrin in neural migration during olfactory development, likely secondary to organization of the radial glial scaffold.

Biology of the Cell, 1999

Annals of the New York Academy of Sciences, 1998

or biochemical approaches associated with in vitro models allows us to study the potential role o... more or biochemical approaches associated with in vitro models allows us to study the potential role of each laminin isoform in basement membrane assembly, cell migration, or cell differentiation.