A physical force may expose Hox genes to express in a morphogenetic density gradient.

In both invertebrates and vertebrates, a set of homeobox genes is involved in the primary pattern formation along the anterior-posterior axis of the developing organism. In particular, the genes of the Hox/HOM complex are located in a physical order in the 3' to 5' direction of the gene clusters. Furthermore, the vertebrate genes of the Hoxa and Hoxd clusters are expressed following the empirical rules of temporal and spatial collinearities: the genes are expressed one after the other according to their positional order and their domains of expression start anteriorly and move gradually towards more posterior locations along the developmental axis. The mechanism that controls this remarkable expression behaviour remains elusive. A proposed morphogen gradient model could justify the serial gene expression in space and time during vertebrate limb development. It is therefore likely that a morphogen concentration ordering might cause the sequential gene expression. I put forward this hypothesis and explore some possibilities that concentration-dependent physical forces might push the Hoxa,d clusters to an environment where the transcriptional activity of the genes is possible. The suggested mechanisms offer satisfactory concentration resolution for differential gene expression. Some experiments are proposed to test the presence of such forces. The verification of this hypothesis would provide a solution to the interpretation problem of the positional information theory in development. Furthermore, it would broaden our knowledge of how gene transcription can be triggered.