Biomedical subjects

Dirk Dormann

Publications and source records attributed to Dirk Dormann.

5 recordsLinked to original sources

PubMed2003

Chemotactic cell movement during development.

Chemotaxis is an important mechanism controlling cell migration over either short or long distances during different developmental processes. Small rapid diffusing chemo-attractants are detected through serpentine, G protein coupled receptors through graded activation of receptors along the length of the cell. Internal amplification results in polarisation of the actin and myosin cytoskeletal dynamics along the gradient and directed movement. The dynamics of these processes can now be studied in individual cells in developing organisms. Slow diffusing chemo-attractants such as growth factors, providing short-range guidance information, often signal through tyrosine kinase receptors. Detection of these signals may involve the active extension of very long cellular process up growth factor gradients, followed by translocation of the cell in the direction of the gradient.

Animals↗

PubMed2002

Visualizing PI3 kinase-mediated cell-cell signaling during Dictyostelium development.

BACKGROUND: Starving amoebae of Dictyostelium discoideum communicate by relaying extracellular cAMP signals, which direct chemotactic movement, resulting in the aggregation of thousands of cells into multicellular aggregates. Both cAMP relay and chemotaxis require the activation of PI3 kinase signaling. The spatiotemporal dynamics of PI3 kinase signaling can be followed in individual cells via the cAMP-induced membrane recruitment of a GFP-tagged PH domain-containing protein, CRAC, which is required for the activation of adenylylcyclase. RESULTS: We show that polarized periodic CRAC-GFP translocation occurs during the aggregation and mound stages of development in response to periodic cAMP signals. The duration of CRAC translocation to the membrane is determined by the duration of the rising phase of the cAMP signal. The system shows rapid adaptation and responds to the rate of change of the extracellular cAMP concentration. When the cells are in close contact, it takes 10 s for the signal to propagate from one cell to the next. In slugs, all cells show a permanent polarized PI3 kinase signaling in their leading edge, which is dependent on cell-cell contact. CONCLUSIONS: Measuring the redistribution of GFP-tagged CRAC has enabled us to study the dynamics of PI3 kinase-mediated cell-cell communication at the individual cell level in the multicellular stages of Dictyostelium development. This approach should also be useful to study the interactions between cell-cell signaling, cell polarization, and movement in the development of other organisms.

Animals↗

PubMed2002

Simultaneous quantification of cell motility and protein-membrane-association using active contours.

We present a new method for the quantification of dynamic changes in fluorescence intensities at the cell membrane of moving cells. It is based on an active contour method for cell-edge detection, which allows tracking of changes in cell shape and position. Fluorescence intensities at specific cortical subregions can be followed in space and time and correlated with cell motility. The translocation of two GFP tagged proteins (CRAC and GRP1) from the cytosol to the membrane in response to stimulation with the chemoattractant cAMP during chemotaxis of Dictyostelium cells and studies of the spatio-temporal dynamics of this process exemplify the method: We show that the translocation can be correlated with motility parameters and that quantitative differences in the rate of association and dissociation from the membrane can be observed for the two PH domain containing proteins. The analysis of periodic CRAC translocation to the leading edge of a cell responding to natural cAMP waves in a mound demonstrates the power of this approach. It is not only capable of tracking the outline of cells within aggregates in front of a noisy background, but furthermore allows the construction of spatio-temporal polar plots, capturing the dynamics of the protein distribution at the cell membrane within the cells' moving co-ordinate system. Compilation of data by means of normalised polar plots is suggested as a future tool, which promises the so-far impossible practicability of extensive statistical studies and automated comparison of complex spatio-temporal protein distribution patterns.

Algorithms↗

PubMed2002

Cell movement patterns during gastrulation in the chick are controlled by positive and negative chemotaxis mediated by FGF4 and FGF8.

During gastrulation in amniotes, epiblast cells ingress through the primitive streak and migrate away to form endodermal, mesodermal, and extraembryonic structures. Here we analyze the detailed movement trajectories of cells emerging at different anterior-posterior positions from the primitive streak, using in vivo imaging of the movement of GFP-tagged streak cells. Cells emerging at different anterior-posterior positions from the streak show characteristic cell migration patterns, in response to guidance signals from neighboring tissues. Streak cells are attracted by sources of FGF4 and repelled by sources of FGF8. The observed movement patterns of anterior streak cells can be explained by an FGF8-mediated chemorepulsion of cells away from the streak followed by chemoattraction toward an FGF4 signal produced by the forming notochord.

Animals↗

PubMed2002

Autoreactive T cell responses in pemphigus and pemphigoid.

Pemphigus and pemphigoid are cutaneous autoimmune diseases characterised by autoantibodies directed against specific adhesion proteins of the epidermis and dermal-epidermal junction. These proteins are usually associated with desmosomes or hemidesmosomes. Binding of antibodies to their targets leads to the loss of cell-cell or cell-matrix adhesion and subsequently to blister formation. The humoral aspects of the autoimmune responses in pemphigus and pemphigoid have been extensively studied in the past. More recently, the cellular interactions resulting in the formation of autoantibodies and the involvement of autoreactive T cells in these diseases have attracted increased interest. In this review, the current knowledge on T cell involvement in pemphigus and pemphigoid is summarised.

Antigen-Presenting Cells↗