Douglas W. DeSimone

Primary Appointment

  • Professor, Cell Biology

Contact

Research Interest(s)

Cell Adhesion and Adhesion-Dependent Cell Signaling in Vertebrate Morphogenesis

Research Description

Research in the DeSimone laboratory centers on the problem of morphogenesis, which is the process biological systems use to generate form and develop increasingly complex structures needed to carry out the specialized functions of tissues, organs and whole organisms. We are interested in elucidating how the "linear" information encoded in genomes is played out over time to yield the fantastic variety of 3-dimensional biological form that we associate with all multi-celled organisms. Our specific research focus is the regulation of cell adhesion and adhesion-dependent cell signaling pathways important for directing cell motility and cell polarity in amphibian embryos. One central hypothesis is that the embryonic extracellular matrix (ECM) serves to define compartments within which cell movements are confined and regulated. We have established that integrin-ECM interactions are a necessary component of the cellular machinery regulating collective cell migration and the radial and mediolateral cell-intercalation behaviors that drive midline convergence and axial extension at gastrulation. In recent years our studies have focused increasingly on the signaling “crosstalk” between cadherin adhesions at cell-cell interfaces and integrin adhesions to the ECM. We have determined that tugging forces on cadherin adhesions are required to establish the polarized protrusions of collectively migrating cells. Current research seeks to elucidate the instructive importance of mechanical signals in directing morphogenetic behaviors of cells and tissues and related mechanisms of adhesion-dependent mechanotransduction. We anticipate that basic knowledge derived from such "simple" model systems of morphogenetic change will be critical to advancing the field of regenerative medicine and the practical applications of tissue engineering.

Selected Publications

  • Bjerke M, Dzamba B, Wang C, DeSimone D. FAK is required for tension-dependent organization of collective cell movements in Xenopus mesendoderm. Developmental biology. 2014;394(2): 340-56. PMID: 25127991 | PMCID: PMC4172504
  • DeSimone D, Horwitz A. Cell Biology. Many modes of motility. Science (New York, N.Y.). 2014;345(6200): 1002-3. PMID: 25170137
  • Rozario T, Mead P, DeSimone D. Diverse functions of kindlin/fermitin proteins during embryonic development in Xenopus laevis. Mechanisms of development. 2014;133 203-17. PMID: 25173804
  • Batra N, Burra S, Siller-Jackson A, Gu S, Xia X, Weber G, DeSimone D, Bonewald L, Lafer E, Sprague E, Schwartz M, Jiang J. Mechanical stress-activated integrin α5β1 induces opening of connexin 43 hemichannels. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(9): 3359-64. PMID: 22331870 | PMCID: PMC3295295
  • Wei S, Xu G, Bridges L, Williams P, Nakayama T, Shah A, Grainger R, White J, DeSimone D. Roles of ADAM13-regulated Wnt activity in early Xenopus eye development. Developmental biology. 2012;363(1): 147-54. PMID: 22227340 | PMCID: PMC3288294
  • Xu G, Wei S, White J, DeSimone D. Identification and characterization of ADAM41, a novel ADAM metalloproteinase in Xenopus. The International journal of developmental biology. 2012;56(5): 333-9. PMID: 22811267 | PMCID: PMC3695402
  • Schwarzbauer J, DeSimone D. Fibronectins, their fibrillogenesis, and in vivo functions. Cold Spring Harbor perspectives in biology. 2011;3(7). PMID: 21576254 | PMCID: PMC3119908
  • Weber G, Bjerke M, DeSimone D. A mechanoresponsive cadherin-keratin complex directs polarized protrusive behavior and collective cell migration. Developmental cell. 2011;22(1): 104-15. PMID: 22169071 | PMCID: PMC3264825
  • Weber G, Bjerke M, DeSimone D. Integrins and cadherins join forces to form adhesive networks. Journal of cell science. 2011;124 1183-93. PMID: 21444749 | PMCID: PMC3115772
  • Wei S, Whittaker C, Xu G, Bridges L, Shah A, White J, Desimone D. Conservation and divergence of ADAM family proteins in the Xenopus genome. BMC evolutionary biology. 2010;10 211. PMID: 20630080 | PMCID: PMC3055250
  • Wei S, Xu G, Bridges L, Williams P, White J, DeSimone D. ADAM13 induces cranial neural crest by cleaving class B Ephrins and regulating Wnt signaling. Developmental cell. 2010;19(2): 345-52. PMID: 20708595 | PMCID: PMC2951023
  • Dzamba B, Jakab K, Marsden M, Schwartz M, DeSimone D. Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization. Developmental cell. 2009;16(3): 421-32. PMID: 19289087 | PMCID: PMC2682918
  • Rozario T, DeSimone D. The extracellular matrix in development and morphogenesis: a dynamic view. Developmental biology. 2009;341(1): 126-40. PMID: 19854168 | PMCID: PMC2854274
  • Rozario T, Dzamba B, Weber G, Davidson L, DeSimone D. The physical state of fibronectin matrix differentially regulates morphogenetic movements in vivo. Developmental biology. 2009;327(2): 386-98. PMID: 19138684 | PMCID: PMC2829434
  • Davidson L, Dzamba B, Keller R, Desimone D. Live imaging of cell protrusive activity, and extracellular matrix assembly and remodeling during morphogenesis in the frog, Xenopus laevis. Developmental dynamics : an official publication of the American Association of Anatomists. 2008;237(10): 2684-92. PMID: 18629871 | PMCID: PMC2628587
  • Schwartz M, DeSimone D. Cell adhesion receptors in mechanotransduction. Current opinion in cell biology. 2008;20(5): 551-6. PMID: 18583124 | PMCID: PMC2581799
  • Thorne B, Bailey A, DeSimone D, Peirce S. Agent-based modeling of multicell morphogenic processes during development. Birth defects research. Part C, Embryo today : reviews. 2008;81(4): 344-53. PMID: 18228259
  • DeSimone D, Dzamba B, Davidson L. Using Xenopus embryos to investigate integrin function. Methods in enzymology. 2007;426 403-14. PMID: 17697893
  • Robertson S, Smith C, Langhans A, McLinden S, Oberhardt M, Jakab K, Dzamba B, DeSimone D, Papin J, Peirce S. Multiscale computational analysis of Xenopus laevis morphogenesis reveals key insights of systems-level behavior. BMC systems biology. 2007;1 46. PMID: 17953751 | PMCID: PMC2190763
  • Davidson L, Marsden M, Keller R, Desimone D. Integrin alpha5beta1 and fibronectin regulate polarized cell protrusions required for Xenopus convergence and extension. Current biology : CB. 2006;16(9): 833-44. PMID: 16682346
  • Alfandari D, Cousin H, Gaultier A, Hoffstrom B, DeSimone D. Integrin alpha5beta1 supports the migration of Xenopus cranial neural crest on fibronectin. Developmental biology. 2003;260(2): 449-64. PMID: 12921745
  • Marsden M, DeSimone D. Integrin-ECM interactions regulate cadherin-dependent cell adhesion and are required for convergent extension in Xenopus. Current biology : CB. 2003;13(14): 1182-91. PMID: 12867028
  • Na J, Marsden M, DeSimone D. Differential regulation of cell adhesive functions by integrin alpha subunit cytoplasmic tails in vivo. Journal of cell science. 2003;116 2333-43. PMID: 12711704
  • Davidson L, Hoffstrom B, Keller R, DeSimone D. Mesendoderm extension and mantle closure in Xenopus laevis gastrulation: combined roles for integrin alpha(5)beta(1), fibronectin, and tissue geometry. Developmental biology. 2002;242(2): 109-29. PMID: 11820810
  • Smith K, Gaultier A, Cousin H, Alfandari D, White J, DeSimone D. The cysteine-rich domain regulates ADAM protease function in vivo. The Journal of cell biology. 2002;159(5): 893-902. PMID: 12460986 | PMCID: PMC2173380
  • Alfandari D, Cousin H, Gaultier A, Smith K, White J, Darribère T, DeSimone D. Xenopus ADAM 13 is a metalloprotease required for cranial neural crest-cell migration. Current biology : CB. 2001;11(12): 918-30. PMID: 11448768
  • Marsden M, DeSimone D. Regulation of cell polarity, radial intercalation and epiboly in Xenopus: novel roles for integrin and fibronectin. Development (Cambridge, England). 2001;128(18): 3635-47. PMID: 11566866
  • Cohen M, Hoffstrom B, DeSimone D. Active zones on motor nerve terminals contain alpha 3beta 1 integrin. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2000;20(13): 4912-21. PMID: 10864949
  • Lallier T, DeSimone D. Separation of neural induction and neurulation in Xenopus. Developmental biology. 2000;225(1): 135-50. PMID: 10964470