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 d eveloping organism. In particular, the genes of the Hox/HOM complex are loc ated in a physical order in the 3' to 5' direction of the gene clusters. Fu rthermore, the vertebrate genes of the Horn and Herd 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 toward s 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 concent ration-dependent physical forces might push the Hoxa,d clusters to an envir onment where the transcriptional activity of the genes is possible. The sug gested mechanisms offer satisfactory concentration resolution for different ial gene expression. Some experiments are proposed to test the presence of such forces. The verification of this hypothesis would provide a solution t o the interpretation problem of the positional information theory in develo pment. Furthermore, it would broaden our knowledge of how gene transcriptio n can be triggered. (C) 2001 Society for Mathematical Biology.