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Jesse Roman

Bio: Jesse Roman is an academic researcher from Washington University in St. Louis. The author has contributed to research in topics: Fibronectin & Actin. The author has an hindex of 7, co-authored 7 publications receiving 778 citations.

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Journal ArticleDOI
26 Jun 1992-Cell
TL;DR: Evidence that an integrin (VLA-4) and its counter receptor (VCAM-1) have a role in secondary myogenesis is provided and patterns suggest that VLA-3-VCAM1 interactions influence alignment of secondary myoblasts along primary myotubes and/or the fusion of secondaryMyoblasts.

407 citations

Journal ArticleDOI
TL;DR: McDonald et al. as discussed by the authors used peptide antibodies specifically recognizing the alpha 5 subunit of the very late antigens (VLAs) subgroup of the integrin family.
Abstract: Cells interact with extracellular fibronectin (FN) via adhesive fibronectin receptors (FNRs) that are members of the very late antigens (VLAs) subgroup of the integrin family. In stationary fibroblasts, the FNR is highly organized and distributed identically to extracellular FN fibrils. However, in highly migratory neural crest cells and embryonic somatic fibroblasts, this organization is lost and the FNR appears diffuse. Similarly, oncogenic transformation typically leads to disorganization of the FN receptor and loss of matrix FN. Two models can account for these observations. First, the FN matrix may organize the FN receptor at extracellular matrix contacts on the cell surface. Motile cells not depositing FN matrices thus lack organized receptors. Alternatively, as the FNR is required for optimal FN matrix assembly, (McDonald, J. A., B. J. Quade, T. J. Broekelmann, R. LaChance, K. Forseman, K. Hasegawa, and S. Akiyama. 1987. J. Biol. Chem. 272:2957-2967; Roman, J. R. M. LaChance, T. J. Broekelmann, C. J. R. Kennedy, E. A. Wayner, W. G. Carter, J. A. McDonald. 1989. J. Cell Biol. 108:2529-2543) and has putative cytoskeletal links, it could be organized from within the cell helping to position newly forming FN fibrils. To study this question, we developed peptide antibodies specifically recognizing the alpha 5 subunit of the FNR. Using these antibodies, we examined the organization of FN and of the FNR in normal, matrix assembly inhibited, and SV40-transformed human fibroblasts. On FN-coated substrates, the FNR is found in focal contacts rather than diffusely on the basal cell surface, suggesting FNR interaction with intracellular components. However, when FN fibrils are deposited, the FNR is co-distributed with these fibrils. Preventing FN matrix assembly prevents organization of the FNR. Moreover, when fibroblasts with well established FN matrices and co-distributed FNR are incubated briefly with monoclonal antibodies that block FNR binding to FN, the FNR is no longer co-distributed with the FN matrix. Thus, the FN receptor is organized in fibrils on the cell surface in response to extracellular FN. Because exogenous FN restores a FN matrix and receptor organization to SV40-transformed cells, the diffuse FN receptor phenotype appears to be related to loss of the FN matrix rather than to impaired FNR function. These results explain diffusely distributed FNRs in migratory neural crest and embryonic fibroblasts lacking well organized FN matrices and emphasize the existence of separate but related systems controlling FN deposition and recognition by receptor-armed cells.

148 citations

Journal ArticleDOI
TL;DR: The distribution of FN and the α5 subunit of its receptor, the integrin α5β1, in the lungs and hearts of murine embryos at 11, 13, 16, and 18 days of gestation suggest a role in organogenesis.
Abstract: The developmentally regulated expression of fibronectin (FN) in developing organs and FN's ability to stimulate cell migration and differentiation in vitro suggest a role in organogenesis. We examined the distribution of FN and the α5 subunit of its receptor, the integrin α5β1, in the lungs and hearts of murine embryos at 11, 13, 16, and 18 days of gestation. In the lung, FN staining was present in the mesenchyme and parabronchial cells at day 11, increased at day 13, and decreased after day 16. Increases in FN coincided with the period of branching morphogenesis, and FN was concentrated at areas of airway bifurcation, suggesting a role for FN in cleft formation. The α5 subunit appeared later at 13 days, co-distributing with FN only in well-developed primary bronchioles. At all stages, α-smooth muscle actin expression correlated temporally and spatially with that of the α5 subunit. In the heart, staining for FN, the α5 subunit, and α-smooth muscle actin were present at day 11 and increased at day 13. FN w...

102 citations

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TL;DR: The data suggest that taspine promotes early phases of wound healing in a dose-dependent manner with no substantial modification thereafter, and is probably related to its chemotactic properties on fibroblasts and is not mediated by changes in extracellular matrix.
Abstract: Taspine (mol wt 369,000) is an alkaloid extracted from trees of Croton (family Euphorbiaceae) of the western Amazon region that has been used by natives and others as a vulnerary agent. Taspine was purified from tree sap to test its healing properties using different topical concentrations in the paired rat surgical incision model. Wound tensile strength and histology were evaluated. Samples treated with 250 micrograms, but not those treated with 50 micrograms or 10 micrograms, had significant higher values for MBS than paired controls (26%, P < 0.005, and 30%, P < 0.001, by Days 5 and 7, respectively). Taspine did not modify MBS at Day 12. Sample treated with 250 micrograms had significantly greater mononuclear cellular infiltration at Days 5 and 7 but not at Day 12. To better understand the effect of taspine as an enhancer of wound healing, we conducted in vitro studies in cell cultures. Taspine stimulated chemotaxis for fibroblasts. Taspine did not have an effect on specific assays for macrophage chemotaxis, neutrophil activation, fibroblast proliferation, or matrix assembly. Taken together, the data suggest that taspine promotes early phases of wound healing in a dose-dependent manner with no substantial modification thereafter. Its mechanism of action is probably related to its chemotactic properties on fibroblasts and is not mediated by changes in extracellular matrix.

83 citations


Cited by
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TL;DR: For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved the understanding of skeletal muscle biology, with focuses on functions of satellite cells and their niche during the process ofletal muscle regeneration.
Abstract: Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process invol...

1,585 citations

Journal ArticleDOI
TL;DR: The data indicate that VCAM-1 plays a dominant role in the initiation of atherosclerosis in mice generated from heterozygous intercrosses and fed a cholesterol-enriched diet for 8 weeks.
Abstract: VCAM-1 and ICAM-1 are endothelial adhesion molecules of the Ig gene superfamily that may participate in atherogenesis by promoting monocyte accumulation in the arterial intima. Both are expressed in regions predisposed to atherosclerosis and at the periphery of established lesions, while ICAM-1 is also expressed more broadly. To evaluate functions of VCAM-1 in chronic disease, we disrupted its fourth Ig domain, producing the murine Vcam1D4D allele. VCAM-1D4D mRNA and protein were reduced to 2–8% of wild-type allele (Vcam1+) levels but were sufficient to partially rescue the lethal phenotype of VCAM-1–null embryos. After crossing into the LDL receptor–null background, Vcam1+/+ and Vcam1D4D/D4D paired littermates were generated from heterozygous intercrosses and fed a cholesterol-enriched diet for 8 weeks. The area of early atherosclerotic lesions in the aorta, quantified by en face oil red O staining, was reduced significantly in Vcam1D4D/D4D mice, although cholesterol levels, lipoprotein profiles, and numbers of circulating leukocytes were comparable to wild-type. In contrast, deficiency of ICAM-1 either alone or in combination with VCAM-1 deficiency did not alter nascent lesion formation. Therefore, although expression of both VCAM-1 and ICAM-1 is upregulated in atherosclerotic lesions, our data indicate that VCAM-1 plays a dominant role in the initiation of atherosclerosis.

1,149 citations

Journal ArticleDOI
TL;DR: Cloned Drosophila homologs of rac and CDC42, Drac1, and Dcdc42 proteins cause qualitatively distinct morphological defects, suggesting that similar GTPases in the same subfamily have unique roles in morphogenesis.
Abstract: The small GTPases of the Rac/Rho/Cdc42 subfamily are implicated in actin cytoskeleton-membrane interaction in mammalian cells and budding yeast. The in vivo functions of these GTPases in multicellular organisms are not known. We have cloned Drosophila homologs of rac and CDC42, Dracl, and Dcdc42. They share 70% amino acid sequence identity with each other, and both are highly expressed in the nervous system and mesoderm during neuronal and muscle differentiation, respectively. We expressed putative constitutively active and dominant-negative Dracl proteins in these tissues. When expressed in neurons, Dracl mutant proteins cause axon outgrowth defects in peripheral neurons without affecting dendrites. When expressed in muscle precursors, they cause complete failure of, or abnormality in, myoblast fusion. Expressions of analogous mutant Dcdc42 proteins cause qualitatively distinct morphological defects, suggesting that similar GTPases in the same subfamily have unique roles in morphogenesis.

988 citations

Journal ArticleDOI
TL;DR: A large heparan sulfate proteoglycan, important for charge‐dependent molecular sieving, is firmly anchored in the basement membrane and can bind itself through a core‐protein interaction to form dimers and oligomers and bind laminin and type IV collagen through its glycosaminoglycan chains.
Abstract: Basement membranes are specialized extracellular matrices with support, sieving, and cell regulatory functions. The molecular architectures of these matrices are created through specific binding interactions between unique glycoprotein and proteoglycan protomers. Type IV collagen chains, using NH2-terminal, COOH-terminal, and lateral association, form a covalently stabilized polygonal framework. Laminin, a four-armed glycoprotein, self-assembles through terminal-domain interactions to form a second polymer network, Entactin/nidogen, a dumbbell-shaped sulfated glycoprotein, binds laminin near its center and interacts with type IV collagen, bridging the two. A large heparan sulfate proteoglycan, important for charge-dependent molecular sieving, is firmly anchored in the basement membrane and can bind itself through a core-protein interaction to form dimers and oligomers and bind laminin and type IV collagen through its glycosaminoglycan chains. Heterogeneity of structure and function occur in different tissues, in development, and in response to different physiological needs. The molecular architecture of these matrices may be regulated during or after primary assembly through variations in compositions, isoform substitutions, and the modifying influence of exogenous macromolecules such as heparin and heparan sulfate.

941 citations

Journal ArticleDOI
TL;DR: The results raise the possibility of abortifacients targeting alpha 4 integrins, and raise serious questions about potential side effects of drugs currently being designed to blockalpha 4 integrin functions in inflammation.
Abstract: alpha 4 integrins are cell surface receptors that mediate cell-extracellular matrix (ECM) and cell-cell adhesions by interacting with fibronectin (FN) and vascular cell adhesion molecule 1 (VCAM-1), respectively. We have generated a null mutation in the gene for the alpha 4 integrin subunit. Homozygous null embryos express no alpha 4 integrins and show two unexpected defects, both of which lead to embryonic lethality. The first defect is failure of fusion of the allantois with the chorion during placentation. The second is in the development of the epicardium and coronary vessels leading to cardiac hemorrhage. Both processes clearly involve alpha 4 integrin interactions that were previously unsuspected. alpha 4 integrin and VCAM-1 are expressed at the sites of these interactions. These results raise the possibility of abortifacients targeting alpha 4 integrins, and raise serious questions about potential side effects of drugs currently being designed to block alpha 4 integrin functions in inflammation.

809 citations