Abstract

Vertebrate Hox genes are essential for the proper organization of the body plan during development. Inactivation of these genes usually leads to important alterations, or transformations, in the identities of the affected developing structures. Hox genes are activated in a progressive temporal sequence which is colinear with the position of these genes on their respective complexes, so that 'anterior' genes are activated earlier than 'posterior' ones (temporal colinearity). Here, an hypothesis is considered in which the correct timing of activation of this gene family is necessary in order to properly establish the various expression domains. Slight modifications in the respective times of gene activation (heterochronies) may shift expression domains along the rostrocaudal axis and thus induce concurrent changes in morphologies. It is further argued that temporal colinearity only occurs in cells with high mitotic rates, which results in a strong linkage between patterning and growth control and makes the patterning process unidirectional, from anterior, proximal and early, to posterior, distal and late, a model referred to as the 'Einbahnstrasse'. While the nature of the mechanism(s) behind temporal and spatial colinearities is unknown, it is proposed that such a mechanism relies on meta-cis interactions, that is it may necessitate gene contiguity. Such a mechanism would be based on DNA-specific, rather than gene-specific, features such as chromatin configurations or DNA replication. The existence of such a meta-cis mechanism would explain the extraoridinary conservation of this genetic system during evolution as its basic properties would be linked to that of the genetic material itself.(ABSTRACT TRUNCATED AT 250 WORDS)

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