A model is proposed that deals with the observed collinearities (spatial, temporal and quantitative) of Hox gene expression during pattern formation along the primary and secondary axes of vertebrates. In particular, in the proximodistal axis of the developing limb, it is assumed that a morphogen gradient is laid down with its source at the distal tip of the bud. The extracellular signals in every cell of the morphogenetic field are transduced and uniformly amplified so that molecules are produced in the (...) nucleus with appropriate physicochemical properties. These molecules can exert a concentration‐dependent force on the Hox cluster. It is assumed that, before activation, the Hox cluster is packaged as an elongated rigid body inside the chromatin and is covered by a coat that prevents the transcription factors reaching the genes of the cluster. The transcription factors are confined to the interchromatin domain and their density decreases with their distance from the chromatin surface. A gradual increase in the extracellular morphogen concentration causes a corresponding increase in the number of the nuclear molecules and the resulting bigger force pushes the Hox cluster toward the interchromatin domain. The step‐by‐step translocations of the Hox cluster initiate the consecutive exposure of genes to their transcription factors. The model explains how gene activation is triggered and it describes spatial, temporal and quantitative collinearities at the initial stages of gene expression. Some recent experiments of Hox deletions and duplications are accounted for by the model. BioEssays 26:189–195, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

During vertebrate limb development, various genes of the Hox family, the products of which influence skeletal element identity, are expressed in specific spatiotemporal patterns in the limb bud mesenchyme. At the same time, the cells also exhibit ‘self‐organizing’ behavior – interacting with each other via extracellular matrix and cell‐cell adhesive molecules to form the arrays of mesenchymal condensations that lead to the cartilaginous skeletal primordia. A recent study by Yokouchi et al.(1) establishes a connection between these phenomena. They misexpressed the (...) product of the Hoxa‐13 gene in chick limb buds and demonstrated both skeletal pattern perturbations and changes in cell‐cell adhesivity in mesenchyme aberrantly expressing this protein. (shrink)

When two populations of cells within a tissue mass differ from one another in magnitude or type of intercellular adhesions, a boundary can form within the tissue, across which cells will fail to mix. This phenomenon may occur regardless of the identity of the molecules that mediate cell adhesion. If, in addition, a choice between the two adhesive states is regulated by a molecule the concentration of which is periodic in space, or in time, then alternating bands of non‐mixing tissue, (...) or segments, can form. But temporal or spatial periodicities in concentration will tend to arise for any molecule that is positively autoregu‐latory. It is therefore proposed that segmentation is a ‘generic’ property of metazoan organisms, and that metamerism would be expected to have emerged numerous times during evolution. A simple model of segmentation, based solely on differential adhesion and periodic regulation of adhesion, can account for segment properties as disparate as those seen in long and short germ band insects, and for diverse experimental results on boundary regeneration in the chick hind brain and the insect cuticle. It is suggested that the complex, multicom‐ponent segment‐forming systems found in contemporary organisms (e.g., Drosophila) are the products of evolutionary recruitment of molecular cues such as homeobox gene products, that increase the reliability and stability of metameric patterns originally templated by generic self‐organizing properties of tissues. (shrink)

Hox proteins are well‐known as developmental transcription factors controlling cell and tissue identity, but recent findings suggest that they are also part of the cell replication machinery. Hox‐mediated control of transcription and replication may ensure coordinated control of cell growth and differentiation, two processes that need to be tightly and precisely coordinated to allow proper organ formation and patterning. In this review we summarize the available data linking Hox proteins to the replication machinery and discuss the developmental and pathological implications (...) of this new facet of Hox protein function. (shrink)