HOX DataBase - NODE01

INTRODUCTION

Since their discovery in 1984, homeo box genes have attracted the attention of molecular biologists, biochemists, genetics, embryologists and evolutionary biologists. This widespread interest reflects the fact that homeobox genes represent the first clear link between all the above fields. Homeobox genes are defined by the presence of a characteristic 183 base pair DNA sequence (the homeobox) coding for a relatively conserved 61amino acid section of protein (the homeodomain).

In mammals the four Homeobox containing gene clusters (HOX-clusters) are a highly conserved group of genes evolutionary related to the Drosophila Antennapedia- and Bithorax-complexes. Extensive analysis of the patterns of gene expression for members from all four of the HOX clusters show that domains of gene expression are spatially restricted in different embryonic sites and axes. An important feature of these homeobox complexes is that there is a linear correlation between the position of a gene in a HOX cluster and its relative Antero-Posterior or axial domain of expression in many embryonic tissues. This property is termed collinearity, and is conserved in arthropods and vertebrates suggesting that regulatory mechanism for controlling the spatially restricted domains of HOX expression are an important feature in maintaining the organization of these gene clusters.

The HOX genes are believed to function in the specification and interpretation of positional information in the embryo through the particular combination of genes (HOX code) that are expressed at any one regional level. This idea is supported by phenotypes arising from experimental perturbation of their expression in vertebrate embryos.

The conservation in expression and regulation suggests that the signals used to establish and maintain HOX expression patterns may also be conserved. Based on a variety of experimental evidence a great deal of interest has focused on possible links between Retinoic Acid (RA) and HOX genes. Many in vitro studies have shown that HOX genes are regulated during RA-induced differentiation of cultured cells. In embryos RA can affect both the patterning of the Limb bud and patterns of HOX expression in the limb. In a number of vertebrates application of RA results in abnormal growth, differentiation and patterning of the nervous system, Neural crest, and bronchial arches which in some cases can be correlated with alterations in HOX expression. Together, the response of the HOX genes to RA in cell culture and embryos, the presence of RA, binding proteins and Receptors in embryos and phenotypic links between RA and HOX expression leads to the suggestion that HOX genes may be targetsfor regulation generated by an RA signaling pathway.