It is commonly assumed that the sum toto of chemotaxis is responsiveness 
to spatial gradients of attractants.  However, in the model system 
Dictyostelium, in which the signal was elegantly visualized over 20 years 
ago by Peter Devreotes and colleagues, the signal is in the form of a 
symmetric, nondissipating wave of cAMP relayed outwardly through a natural 
population of aggregating cells.  This wave has temporal and concentration 
components, as well as spatial components, that all cue cell behavior in the 
chemotactic process.  In the front of each wave, each cell experiences an 
increasing temporal gradient and positive spatial gradient of cAMP; at the
 peak of each wave, each cell experiences a cAMP concentration inhibitory to
 locomotion; and in the back of each wave, each cell experiences a decreasing 
temporal and negative spatial gradient of cAMP.  Cells respond in a unique 
and specific fashion to each of the four phases of the wave, and this sequence
 of behaviors together represents the chemotactic response.  A defect in 
response to any one of the components of the wave compromises natural 
chemotaxis.  Hence, mutants that can efficiently respond to a spatial
 gradient, but not a temporal gradient cannot chemotax in nature (i.e., in
 the natural wave).  Protocols are described to analyze the basic motile
 behavior of cells in the absence of a chemotactic signal, and to test the
 responsiveness of cells to the individual temporal, spatial and concentration
 components of a natural wave.  These protocols include computer-assisted
 methods for analyzing cell behavior developed in the Keck Dynamic Image
 Analysis Facility at Iowa.  The results of mutant analyses using these
 protocols have been used to develop realistic models of cell motility and
 chemotaxis.  These models include independent parallel regulatory pathways
 emanating from different phases of the wave, each affecting a different
 phase-specific behavior.  Results will be presented demonstrating that
 human PMNs possess all of the machinery necessary to read every aspect
 of a wave, like Dictyostelium does, suggesting that signals in the human
 body may be in the form of relayed waves.  Finally, an example will be
 presented of the successful application of this approach to a human
 disease, the Shwachman-Diamond Syndrome.