Gradients and forward spreading of vertebrate Hox gene expression detected by using a Hox/lacZ transgene

Elucidation of the kinetics with which vertebrate Hox expression patterns develop may help us to choose between various models already proposed to explain this process. The chick Hoxa-7/lacZ transgene, expressed in mouse embryos, changes over time in the distribution of its activity along the developing posterior to anterior axis. During an establishment (E) phase (lasting at least up to 10 days) expression is graded from highest levels posteriorly, to low levels anteriorly. Within the graded domain, the overall level of expression spreads forward with time along both neurectoderm and paraxial mesoderm. Spreading in expression is not due to movement of cells, but to increases in both the proportion of lacZ expressing cells and the intensity of expression per cell. By 10.8 days, embryos have reached a late (L) phase in which an anterior up-regulation in expression, together with a posterior down-regulation, cause the graded nature of the expression to be lost. E and L phases are also seen for Hox gene expression detected by in situ hybridization. The switch from E to L occurs at progressively later times as we move 3' to 5' along the Hox cluster. The results are in keeping with models in which Hox genes become differentially expressed according to a graded concentration of an inducer. Binding motifs for the caudal (cdx) proteins, already proposed as such inducers, are conserved in mouse and chick Hoxa-7 enhancer elements.