Integrins: Versatility, modulation, and signaling in cell adhesion, Cell, vol.69, issue.1, pp.11-25, 1992. ,
DOI : 10.1016/0092-8674(92)90115-S
Integrin inactivators: balancing cellular functions in vitro and in vivo, Nature Reviews Molecular Cell Biology, vol.198, issue.7, pp.432-444, 2013. ,
DOI : 10.1083/jcb.201206050
Coordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression, Current Opinion in Genetics & Development, vol.11, issue.1, pp.48-53, 2001. ,
DOI : 10.1016/S0959-437X(00)00155-6
integrin cytodomain, The Journal of Cell Biology, vol.121, issue.3, pp.481-492, 2002. ,
DOI : 10.1016/S0092-8674(00)81392-6
The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal, Nature Cell Biology, vol.43, issue.8, pp.877-883, 2011. ,
DOI : 10.1038/ng.722
The Drosophila Mst Ortholog, hippo, Restricts Growth and Cell Proliferation and Promotes Apoptosis, Cell, vol.114, issue.4, pp.457-467, 2003. ,
DOI : 10.1016/S0092-8674(03)00557-9
TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins, The EMBO Journal, vol.19, issue.24, pp.6778-6791, 2000. ,
DOI : 10.1093/emboj/19.24.6778
Yap1 Acts Downstream of ??-Catenin to Control Epidermal Proliferation, Cell, vol.144, issue.5, pp.782-795, 2011. ,
DOI : 10.1016/j.cell.2011.02.031
Mechanisms of Hippo pathway regulation, Genes & Development, vol.30, issue.1, pp.1-17, 2016. ,
DOI : 10.1101/gad.274027.115
Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis, Genes & Development, vol.26, issue.1, pp.54-68, 2012. ,
DOI : 10.1101/gad.173435.111
Adhesion to fibronectin regulates Hippo signaling via the FAK???Src???PI3K pathway, The Journal of Cell Biology, vol.9, issue.3, pp.503-515, 2015. ,
DOI : 10.1101/gad.173435.111
Cell tension, matrix mechanics, and cancer development, Cancer Cell, vol.8, issue.3, pp.175-176, 2005. ,
DOI : 10.1016/j.ccr.2005.08.009
Regulation of anchorage-dependent signal transduction by protein kinase A and p21-activated kinase, Nature Cell Biology, vol.2, issue.9, pp.593-600, 2000. ,
DOI : 10.1038/35023536
cAMP/PKA signalling reinforces the LATS???YAP pathway to fully suppress YAP in response to actin cytoskeletal changes, The EMBO Journal, vol.74, issue.11, pp.1543-1555, 2013. ,
DOI : 10.1073/pnas.1110428108
Adhesion to fibronectin regulates Hippo signaling via the FAK???Src???PI3K pathway, The Journal of Cell Biology, vol.9, issue.3, pp.503-515, 2015. ,
DOI : 10.1101/gad.173435.111
Role of YAP/TAZ in mechanotransduction, Nature, vol.13, issue.7350, pp.179-183, 2011. ,
DOI : 10.1038/nm1519
Multiparametric Analysis of Cell Shape Demonstrates that ?-PIX Directly Couples YAP Activation to Extracellular Matrix Adhesion mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane, Cell Syst J Cell Biol, vol.4, issue.171, pp.84-96, 2005. ,
Integrin-dependent activation of MAP kinase: a link to shape-dependent cell proliferation., Molecular Biology of the Cell, vol.6, issue.3, pp.273-282, 1995. ,
DOI : 10.1091/mbc.6.3.273
Control of Proliferation and Cancer Growth by the Hippo Signaling Pathway, Molecular Cancer Research, vol.14, issue.2, pp.127-140, 2016. ,
DOI : 10.1158/1541-7786.MCR-15-0305
Integrin signalling regulates YAP and TAZ to control skin homeostasis, Development, vol.143, issue.10, pp.1674-1687, 2016. ,
DOI : 10.1242/dev.133728
Somatic activation of the K-ras oncogene causes early onset lung cancer in mice, Nature, vol.410, issue.6832, pp.1111-1116, 2001. ,
DOI : 10.1038/35074129
Hippo-Independent Activation of YAP by the GNAQ Uveal Melanoma Oncogene through a Trio-Regulated Rho GTPase Signaling Circuitry, Cancer Cell, vol.25, issue.6, pp.831-845, 2014. ,
DOI : 10.1016/j.ccr.2014.04.016
Yap- and Cdc42-Dependent Nephrogenesis and Morphogenesis during Mouse Kidney Development, PLoS Genetics, vol.8, issue.3, 2013. ,
DOI : 10.1371/journal.pgen.1003380.s016
Single-molecule tracking of small GTPase Rac1 uncovers spatial regulation of membrane translocation and mechanism for polarized signaling, Proceedings of the National Academy of Sciences, vol.262, issue.3, pp.267-276, 2015. ,
DOI : 10.1371/journal.pone.0007724
Translocation of cortactin to the cell periphery is mediated by the small GTPase Rac1, J Cell Sci, vol.111, pp.2433-2443, 1998. ,
Dissecting Activation of the PAK1 Kinase at Protrusions in Living Cells, Journal of Biological Chemistry, vol.18, issue.36, pp.24133-24143, 2009. ,
DOI : 10.1016/j.jmb.2006.06.017
Temporal and Spatial Distribution of Activated Pak1 in Fibroblasts, The Journal of Cell Biology, vol.18, issue.7, pp.1449-1458, 2000. ,
DOI : 10.1128/MCB.18.4.2153
Integrin alpha3beta1- dependent activation of FAK/Src regulates Rac1-mediated keratinocyte polarization on, 2007. ,
Activation of Rac1 by Src-dependent phosphorylation of Dock180(Y1811) mediates PDGFR?-stimulated glioma tumorigenesis in mice and humans, and Pan, D. (2013) Spatial organization of Hippo signaling at the plasma membrane mediated by the tumor suppressor Merlin/NF2, pp.1342-1355, 2011. ,
The Nf2 Tumor Suppressor, Merlin, Functions in Rac-Dependent Signaling, Developmental Cell, vol.1, issue.1, pp.63-72, 2001. ,
DOI : 10.1016/S1534-5807(01)00009-0
Angiomotin binding-induced activation of Merlin/NF2 in the Hippo pathway, Cell Research, vol.276, issue.7, pp.801-817, 2015. ,
DOI : 10.1093/nar/22.22.4673
Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors, The Journal of Cell Biology, vol.135, issue.6, pp.1633-1642, 1996. ,
DOI : 10.1083/jcb.135.6.1633
Prognostic value of the Hippo pathway transcriptional coactivators YAP/TAZ and ??1-integrin in conventional osteosarcoma, Oncotarget, vol.7, pp.64702-64710, 2016. ,
DOI : 10.18632/oncotarget.11876
URL : https://hal.archives-ouvertes.fr/hal-01482390
Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by ??3 integrin, The Journal of Cell Biology, vol.266, issue.3, pp.499-509, 2003. ,
DOI : 10.1016/0955-0674(95)80110-3
A combination of Wnt and growth factor signaling induces Arl4c expression to form epithelial tubular structures, The EMBO Journal, vol.33, issue.7, pp.702-718, 2014. ,
DOI : 10.1002/embj.201386942
RhoA Inactivation by p190RhoGAP Regulates Cell Spreading and Migration by Promoting Membrane Protrusion and Polarity, Molecular Biology of the Cell, vol.12, issue.9, pp.2711-2720, 2001. ,
DOI : 10.1091/mbc.12.9.2711
The merlin tumor suppressor localizes preferentially in membrane ruffles, Oncogene, vol.13, pp.1239-1247, 1996. ,
FAK Potentiates Rac1 Activation and Localization to Matrix Adhesion Sites: A Role for betaPIX, Molecular Biology of the Cell, vol.18, issue.1, pp.253-264, 2007. ,
DOI : 10.1091/mbc.E06-03-0207
Epidermal growth factor stimulates Rac activation through Src and phosphatidylinositol 3-kinase to promote colonic epithelial cell migration, AJP: Gastrointestinal and Liver Physiology, vol.294, issue.1, pp.276-285, 2008. ,
DOI : 10.1152/ajpgi.00340.2007
Endocytic Trafficking of Rac Is Required for the Spatial Restriction of Signaling in Cell Migration, Cell, vol.134, issue.1, pp.135-147, 2008. ,
DOI : 10.1016/j.cell.2008.05.034
Paxillin Associates with the Microtubule Cytoskeleton and the Immunological Synapse of CTL through Its Leucine-Aspartic Acid Domains and Contributes to Microtubule Organizing Center Reorientation, The Journal of Immunology, vol.187, issue.11, pp.5824-5833, 2011. ,
DOI : 10.4049/jimmunol.1003690
Integrin-Linked Kinase Controls Microtubule Dynamics Required for Plasma Membrane Targeting of Caveolae, Developmental Cell, vol.19, issue.4, pp.574-588, 2010. ,
DOI : 10.1016/j.devcel.2010.09.007
Fetal and Adult Hematopoietic Stem Cells Require ??1 Integrin Function for Colonizing Fetal Liver, Spleen, and Bone Marrow, Immunity, vol.12, issue.6, pp.653-663, 2000. ,
DOI : 10.1016/S1074-7613(00)80216-2
Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors, Development, vol.133, issue.16, pp.3231-3244, 2006. ,
DOI : 10.1242/dev.02480
Endogenous oncogenic K-rasG12D stimulates proliferation and widespread neoplastic and developmental defects, Endogenous oncogenic K- ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects, pp.375-387, 2004. ,
DOI : 10.1016/S1535-6108(04)00085-6
URL : http://doi.org/10.1016/s1535-6108(04)00085-6
A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow, Nature Protocols, vol.12, issue.1, pp.102-106, 2009. ,
DOI : 10.1038/nprot.2008.221
Defective osteoblast function in ICAP-1-deficient mice, Development, vol.134, issue.14, pp.2615-2625, 2007. ,
DOI : 10.1242/dev.000877
URL : https://hal.archives-ouvertes.fr/inserm-00166116
Osteoblast mineralization requires ??1 integrin/ICAP-1???dependent fibronectin deposition, The Journal of Cell Biology, vol.112, issue.2, pp.307-322, 2011. ,
DOI : 10.1006/dbio.2000.9633
URL : https://hal.archives-ouvertes.fr/inserm-00610020
Circulating fibronectin affects bone matrix, whereas osteoblast fibronectin modulates osteoblast function, J Bone Miner Res, vol.25, pp.706-715, 2009. ,
DOI : 10.1359/jbmr.091011
URL : http://onlinelibrary.wiley.com/doi/10.1359/jbmr.091011/pdf
Integrin-mediated Adhesion of Human Neutrophils, Journal of Biological Chemistry, vol.268, issue.26, pp.24181-24188, 2003. ,
DOI : 10.1073/pnas.061029698
URL : https://hal.archives-ouvertes.fr/hal-00820751
Specificity and Mechanism of Action of EHT 1864, a Novel Small Molecule Inhibitor of Rac Family Small GTPases, Journal of Biological Chemistry, vol.263, issue.49, pp.35666-35678, 2007. ,
DOI : 10.1016/j.tcb.2004.05.003
An Isoform-Selective, Small-Molecule Inhibitor Targets the Autoregulatory Mechanism of p21-Activated Kinase, Chemistry & Biology, vol.15, issue.4, pp.322-331, 2008. ,
DOI : 10.1016/j.chembiol.2008.03.005
Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex 203-216 FIGURE LEGENDS Figure 1. ?1 integrins regulate osteoblast cell proliferation in vivo and in vitro. A. Histo-morphometric analysis of osteoblast number on wild-type (?1 f/f ) and Osx-Cre; ?1 f/f (?1 Ost-KO ) 30-days-old mice tibias. Graphs show the mean ± SD from five independent experiments B. Quantification of apoptotic (TUNEL-positive) and proliferating (BrdU-positive) cells in periosteum and trabecular bone in wild-type and mutant 30-days-old mice tibias (p; periosteum; t; trabecular bone). n=50; statistical significance of differences assessed by a two-tailed unpaired Student's t-test, 3 independent experiments. C. Representative TUNEL staining D. BrdU staining on trabecular bone sections from wild-type and mutant mouse tibias (hc, hypertrophic cartilage; tb, trabecular bone; bm, bone marrow) Scale bar represent 40µm. E. Images of BrdU staining of trabecular bone sections. F. BrdU based quantification of the proliferation rate of ?1f/f, ?1-/-primary mouse embryonic fibroblasts. (statistical significance of differences assessed by a two-tailed unpaired Student's t-test, 3 independent experiments) Cell adhesion control of YAP activation 17 G. In vitro proliferation rate of wild-type (?1 f/f ) and ?1 integrin deficient (?1 -/-) osteoblasts. n=50; statistical significance of differences assessed by a two-tailed unpaired Student's t-test, 3 independent experiments. H. BrdU based quantification of the proliferation rate of ?1 f Statistical significance of differences assessed by a two-tailed unpaired Student's t-test, osteoblasts, or ?1 -/osteoblasts expressing human ?1 integrin (rescue), constitutively active MEK (MEKQ56P), or nuclear active ERK fusion mutant (MEK/ERKLA), 2004. ,
Nuclei were stained with DAPI F. Western blot analysis of YAP phosphorylation. YAP pS127 and total YAP in ?1 f/f and ?1 -/osteoblasts after cell fractionation of the nuclear fraction (N) and cytoplasmic/membrane fraction (CM). Lamin B and tubulin were used as nuclear and cytoplasmic markers ,
CyclinD2 (CCND2), p19Arf and p21CIP (CDKN1A) mRNAs in ?1 -/-and ?1 f/f osteoblasts expressing Flag-YAP 5SA normalized to ?1 f/f osteoblasts, CCND1) ,