Hox Gene Function and the Development of the Head

Abstract

HOM/Hox genes are a family of genes (the homeogene family) that show similarities in structure, organisation into complexes and expression patterns. They code for transcriptional regulators which are thought to function at the top of a genetic hierarchy that controls the relative position of the cells along the embryonic axes. First discovered in Drosophila and then found in vertebrates, they were recently identified in the genome of animals as diverse as nematodes, leeches, amphioxus and hydra, suggesting that a HOM/Hox gene cluster already existed in the common ancestor of all animals. The presence of HOM/Hox cluster(s) has been proposed as one of the characters defining the Kingdom Animalia (i.e. the Zootype: reviewed in Slack, 1993; Holland, 1992; Thorogood, 1993; Kappen et al., 1993). Interphyletic comparisons between insect HOM genes and vertebrate Hox genes are well documented (reviewed in McGinnis and Krumlauf, 1992; Botas, 1993). In vertebrates there are four paralogous clusters of Hox genes, referred to as Hox A, B, C, and D, each showing clear structural homology to the prototypic homeotic complex (HOM-C) of Drosophila. During ontogenesis, Hox genes are expressed in the neurectoderm and paraxial mesoderm in specific but overlapping domains that extend from the caudal end of the embryo to a sharp rostral limit. There is a correlation (termed spatial colinearity) between the position of a Hox gene within its cluster and the location of its rostral limit of expression. Significantly, this spatial colinearity also exists in Drosophila. Both vertebrate Hox and insect HOM gene expression domains respect metameric boundaries. Loss-of-function mutations (i.e. generated by gene disruption) and gain-of-function mutations (i.e. generated by ectopic gene expression) of both mouse Hox genes and Drosophila HOM genes often cause a transformation of specific metameres [serially homologous anatomical units, repeated along the rostrocaudal axis such as somites (mouse) or parasegments (Drosophila)] into the likeness of their neighbours, indicating that these genes are involved in the specification of the phenotype of a given segment according to its position along the rostrocaudal axis. Since the segmented body plans of mouse and Drosophila have arisen totally independently during evolution, it appears that at least part of HOM/Hox genes network has been co-opted to impart morphogenetic segment identity in animal groups employing different segmentation strategies (Holland, 1990).