R. O. Hynes, 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

D. Bouvard, J. Pouwels, N. De-franceschi, and J. Ivaska, 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

R. K. Assoian and M. A. Schwartz, 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

E. Hirsch, L. Barberis, M. Brancaccio, O. Azzolino, D. Xu et al., integrin cytodomain, The Journal of Cell Biology, vol.121, issue.3, pp.481-492, 2002.
DOI : 10.1016/S0092-8674(00)81392-6

B. Zhao, K. Tumaneng, and K. L. Guan, 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

K. F. Harvey, C. M. Pfleger, and I. K. Hariharan, 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

F. Kanai, P. A. Marignani, D. Sarbassova, R. Yagi, R. A. Hall et al., 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

K. Schlegelmilch, M. Mohseni, O. Kirak, J. Pruszak, J. R. Rodriguez et al., 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

Z. Meng, T. Moroishi, and K. L. Guan, Mechanisms of Hippo pathway regulation, Genes & Development, vol.30, issue.1, pp.1-17, 2016.
DOI : 10.1101/gad.274027.115

B. Zhao, L. Li, L. Wang, C. Y. Wang, J. Yu et al., 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

N. Kim and B. M. Gumbiner, 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

S. Huang and D. E. Ingber, 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

A. K. Howe and R. L. Juliano, 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

M. Kim, S. Lee, S. Kuninaka, H. Saya, H. Lee et al., 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

N. G. Kim and B. M. Gumbiner, 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

S. Dupont, L. Morsut, M. Aragona, E. Enzo, S. Giulitti et al., Role of YAP/TAZ in mechanotransduction, Nature, vol.13, issue.7350, pp.179-183, 2011.
DOI : 10.1038/nm1519

J. E. Sero, C. Bakal, T. Okada, M. Lopez-lago, and F. G. Giancotti, 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.

X. Zhu and R. K. Assoian, 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

U. Ehmer and J. Sage, 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

A. Elbediwy, Z. I. Vincent-mistiaen, B. Spencer-dene, R. K. Stone, S. Boeing et al., Integrin signalling regulates YAP and TAZ to control skin homeostasis, Development, vol.143, issue.10, pp.1674-1687, 2016.
DOI : 10.1242/dev.133728

L. Johnson, K. Mercer, D. Greenbaum, R. T. Bronson, D. Crowley et al., 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

X. Feng, M. S. Degese, R. Iglesias-bartolome, J. P. Vaque, A. A. Molinolo et al., 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

A. Reginensi, R. P. Scott, A. Gregorieff, M. Bagherie-lachidan, C. Chung et al., 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

S. Das, T. Yin, Q. Yang, J. Zhang, Y. I. Wu et al., 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

S. A. Weed, Y. Du, and J. T. Parsons, Translocation of cortactin to the cell periphery is mediated by the small GTPase Rac1, J Cell Sci, vol.111, pp.2433-2443, 1998.

M. C. Parrini, J. Camonis, M. Matsuda, and J. De-gunzburg, 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

M. A. Sells, A. Pfaff, C. , and J. , 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

D. P. Choma, V. Milano, K. M. Pumiglia, and C. M. Dipersio, Integrin alpha3beta1- dependent activation of FAK/Src regulates Rac1-mediated keratinocyte polarization on, 2007.

H. Feng, B. Hu, K. W. Liu, Y. Li, X. Lu et al., 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.

R. J. Shaw, J. G. Paez, M. Curto, A. Yaktine, W. M. Pruitt et al., 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

Y. Li, H. Zhou, F. Li, S. W. Chan, Z. Lin et al., 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

S. Miyamoto, H. Teramoto, J. S. Gutkind, and K. M. Yamada, 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

C. Bouvier, N. Macagno, Q. Nguyen, A. Loundou, C. Jiguet-jiglaire et al., 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

R. Faccio, D. V. Novack, A. Zallone, F. P. Ross, and S. L. Teitelbaum, 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

S. Matsumoto, S. Fujii, A. Sato, S. Ibuka, Y. Kagawa et al., 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

W. T. Arthur and K. Burridge, 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

C. Gonzalez-agosti, L. Xu, D. Pinney, R. Beauchamp, W. Hobbs et al., The merlin tumor suppressor localizes preferentially in membrane ruffles, Oncogene, vol.13, pp.1239-1247, 1996.

F. Chang, C. A. Lemmon, D. Park, and L. H. Romer, 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

R. S. Dise, M. R. Frey, R. H. Whitehead, and D. B. Polk, 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

A. Palamidessi, E. Frittoli, M. Garré, M. Faretta, M. Mione et al., 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

L. K. Robertson and H. L. Ostergaard, 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

S. A. Wickstrom, A. Lange, M. W. Hess, J. Polleux, J. P. Spatz et al., 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

A. J. Potocnik, C. Brakebusch, and R. Fässler, 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

S. J. Rodda and A. P. Mcmahon, 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

D. A. Tuveson, A. T. Shaw, N. A. Willis, D. P. Silver, E. L. Jackson et al., 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

M. Soleimani and S. Nadri, 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

D. Bouvard, A. Aszodi, G. Kostka, M. R. Block, C. Albiges-rizo et al., 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

M. Brunner, A. Millon-fremillon, G. Chevalier, I. A. Nakchbandi, D. Mosher et al., 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

A. Bentmann, N. Kawelke, D. Moss, H. Zentgraf, Y. Bala et al., 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

K. Dib, F. Melander, L. Axelsson, M. C. Dagher, P. Aspenström et al., 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

A. Shutes, C. Onesto, V. Picard, B. Leblond, F. Schweighoffer et al., 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

S. W. Deacon, A. Beeser, J. A. Fukui, U. E. Rennefahrt, C. Myers et al., 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

H. Y. Ho, R. Rohatgi, A. M. Lebensohn, M. Le, J. Li et al., 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.

G. Ras and . Mefs, 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

F. Rt, 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)