UNDERSTANDING CELL SIGNALING

Understanding Cell Signaling

Understanding Cell Signaling

Introduction

Development is characterised by a number of cellular processes such as growth, division, cell differentiation and movement all controlled by cell-cell signalling. To study these processes in detail it is advantageous to be able to visualise them with high temporal and spatial resolution in the context of their tissues in vivo. Many of the interesting cellular behaviours such as division, cell shape changes and movement are mediated by precisely controlled local changes in the dynamics of the actin-myosin cytoskeleton, which as a result is the target for many of the known signalling pathways. Cells generally move in response to signals generated by surrounding tissue, however moving cells often signal themselves to their environment and these interactions help the creation of new signalling environments that result in local activation of new gene expression programmes that are an essential part of development. Following cell movement at the tissue level and correlating this with detailed behavioural studies and simultaneous visualisation and measurement of the underlying signalling dynamics controlling the cytoskeleton and adhesion is therefore one of the major challenges in development. In individual cells these signalling pathways and cytoskeletal dynamics can be followed in tremendous detail down to the single molecule level through the use of Total Internal Reflection Microscopy (TIRF) and . Advances being made in multi-photon confocal, and more recently light sheet microscopy starts to allow the investigation of cell behaviours in tissue in vivo and .

We will illustrate the usefulness of some of these methods on some specific examples from our own work on the development of the cellular slime mould Dictyostelium discoideum and the control of cell movement during gastrulation in the chick embryo. The main question that we pursue is how movement is controlled during development, which signals guide the migration of cells, how cells detect these signals and translate them into directed movement.( T. Bretschneider, 2002 642)

Discussion

Dictyostelium is a simple eukaryotic model system that is widely used to study essential cell biological processes such as cell division, chemotactic cell movement and pattern formation. Vegetative cells feed on bacteria and divide by binary fission. Upon starvation a multicellular developmental cycle is initiated in which hundreds of thousands of amoebae can aggregate to form a fruiting body . The process is controlled by chemotaxis to cAMP secreted by cells in aggregation centres . These cells secrete cAMP periodically into the extracellular medium where it diffuses away to neighbouring cells. These cells detect and amplify the signal, secrete it and in turn signal to their neighbours. Binding of cAMP to the cell surface receptors also initiates a desensitisation process which - after a time delay of a few minutes - results in a cessation of cAMP production . This process results in the outward propagation of cAMP waves. Since the cells also show a chemotactic response to cAMP during the rising phase of the cAMP waves, they move in the direction of the source as long as the signal is ...