Hox Genes or Homeotic genes in Development

Homeotic genes/ Hox genes encode transcription factors, which play an important role in giving a unique identity to each segment and thereby setting up morphogenesis along the anterior posterior axis.They are recognizable by the presence of a 60 amino acid long DNA binding region called the homeodomain, but all homeo domain containing proteins are not hox genes. Hox genes exhibit some important properties like:

1) Found in clusters: Hox genes are physically linked on the chromosome. In Drosophila, eight genes are organized in one cluster in flies on third chromosome (Drosophila has four chromosome sets) and whereas four clusters harboring 39 hox genes are found in Humans.

2) Colinearity: The gene order in the cluster mimics the order of expression of genes and their function along the anterior -posterior (A/P) body axis: genes at the 5′ end of the cluster are expressed in, and pattern, the posterior part of the body, whereas genes at the 3′ end pattern the anterior end of the body. In some species ( mainly vertebrates) homeotic genes also exhibit temporal collinearity in addition to spatial…meaning anterior genes exhibit first during development and posterior later.

3) Another important property of Hox genes is that they cause Homeotic transformations , When mutant one metamer or segment gets transformed into likeness of another. For example Ultrabithorax (ubx) which is normally expresses in T3 segment of Drosophila , plays a vital role is formation of Haltere (modified wing) by repressing various wing patterning genes. In flies mutant for ubx halteres are modified into wings and you have a four winged fruit fly.

4) Functional hierarchies among genes in the cluster, called “phenotypic suppression” in Drosophila and posterior prevalence” in vertebrates. Normally genes present in posterior region are dominant over anterior expressing ones meaning posterior most gene (Abdominal B in drosophila) is dominant over all others in complex and labial which is at 3′ end of cluster is least dominant. When cells mutant for particular hox gene ,then the hox gene anterior to the mutant one will now starts expressing in those cells.

Homeotic genes were first discovered in Drosophila and later homologous genes were found in other organisms. Hox genes are evolutionarily conserved and observed in nearly all bilaterans animals most probably originated before Cnidarians ( which have only one anterior and one posterior hox gene representative) and bilaterian split.

Significant amount of research is going on in the field of Hox, but I feel its better to start of with its understanding in fruit fly “Drosophila” . Hox transcription factors specify distinct cell fates along the anterior-posterior (A-P) axis in the fruit fly, Drosophila melanogaster. As said earlier Hox genes are conserved in organisms from cnidarians to humans. In the case of Vertebrates, 39 Hox genes that participate in the developmental control of the nervous system, the skeletal system, the gastrointestinal system, the urogenital system, the blood system, and the limbs. Not surprisingly, mutations and/or mis-expression of Hox factors can cause limb malformations as well as leukemias and cancers.

In Drosophila hox cluster consists of eight genes arranged in two groups referred as Antennapedia complex and Bithorax complex on third chromosome. Antennapedia complex comprises of Labial(lab), Proboscipedia(pb), deformed(dfd), sex combs reduced (scr) and Antennapedia (antp) whereas ultrabithorax(Ubx) ,Abdominal-A(abd-A) and Abdominal-B (Abd-B) forms Bithorax complex. There is split between Antennapedia and ultrabithorax in the hox cluster. However, from an evolutionary and genetic perspective, this is a single cluster that has been physically divided.

Image credit : Hox genes in Humans and mouse @ Openstax