Cell signaling in growth and development: the 11th Annual CABM Symposium, October 8-9, 1997

While many topics were discussed during this symposium, several common themes emerged from the presentations. First, it is increasingly evident that regulation of ligand-receptor interactions is complex and can occur at nearly every conceivable step, including protein processing for release from or tethering to the cell surface, diffusibility through tissues, binding to soluble inhibitors, and competition with antagonists for receptor binding. In particular, the availability of these regulatory steps allows for a range of potential mechanisms by which ligand signaling can be modulated by other protein factors, such as in the case of fringe and its effects on signaling through the Notch receptor. Secondly, a major area of effort in the signaling field will increasingly focus on how cells integrate the signals received from different pathways to coordinate specific developmental responses. For example, as McMahon pointed out, the major signaling pathways that govern the anterior-posterior, dorsal-ventral, and proximal-distal axes of the developing limb bud have now been identified, yet it is completely unclear how these pathways interact to produce positional information in three dimensions. Thirdly, biochemical and structural investigations are now providing insights into the nature of the feedback mechanisms that regulate the strength and duration of activated signals, and how in some cases, these feedback loops can also provide a 'memory' of the signaling response, such as in the case of the adaptation found in bacterial chemotaxis. Finally, the structural analyses of signal transducing molecules remind us of the necessity to understand the mechanistic details of how active and inactive states are maintained, particularly since distant protein modifications can lead to global conformational changes that alter protein activity. These and other general insights underscore the value of broad-based meetings that cut across a range of disciplines and methodologies, such as this CABM symposium, and provide ideas for future directions of investigation.