Organizing axes in time and space; 25 years of colinear tinkering

During vertebrate development, clustered genes from the Hox family of transcription factors are activated in a precise temporal and spatial sequence that follows their chromosomal order (the Hox clock). Recent advances in the knowledge of the underlying mechanisms reveal that the embryo uses a variety of strategies to implement this colinear process, depending on both the type and the evolutionary history of axial structures. The search for a universal mechanism has likely hampered our understanding of this enigmatic phenomenon, which may be caused by various and unrelated regulatory processes, as long as the final distribution of proteins (the HOX code) is preserved.