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 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 restricted. We have established that integrin signaling is involved in the maintenance of planar cell polarity and the regulation of cadherin-based cell-cell adhesion. Thus, we have proposed that integrin-ECM interactions are a necessary component of the cellular machinery regulating the radial and mediolateral cell-intercalation behaviors that drive midline convergence and axial extension in the frog. These studies complement other ongoing work in the laboratory that focuses on mechanisms of cranial neural crest cell migration and the roles of ADAM family membrane metalloproteases. ADAM metalloprotease activity is required for cranial neural crest cell migration by modifying the extracellular matrix that lines the migratory routes of these cells. 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

  • 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