The aim of this project is to study the organisation and function of the Chordate Hox genes, and how. they are regulated. This will be done with the model system of Amphioxus.
The Hox genes are a family of developmental patterning genes. They are clustered in the genome, and their order along the chromosome reflects the order of their expression domains along the embryonic Anteroposterior axis. This is the phenomenon of Colinearity.
Amphioxus is the closest known relative of vertebrates, and is thought to be representative of the vertebrate ancestor. This is because of its simple vertebrate-like body plan. Also Amphioxus has a single Hox gene cluster, whereas vertebrates have four. This lower morphological and genetic complexity should simplify mechanistic analysis, compared to the vertebrates.
I will clone the 5' end of the Amphioxus Hox cluster to check its archetypal nature, and to see whether the even-skipped (eve) homologue is linked to it. This will test hypotheses on the presence/absence of eve in the archetypal metazoan Hox cluster and, along with expression data, test whether Chordate eve genes can act like posterior Hox genes by sharing Hox regulatory elements. Hox gene expression data will also clarify how much of the Amphioxus nerve chord is homologous to the vertebrate brain, a question that has been debated for over 100 years. Expression data will also illuminate possible rules for the Hox genes in patterning the mesoderm of Chordates.
To find the genes that regulate chordate Hox genes I will use transgenic flies, carrying putative Amphioxus regulatory elements cloned upstream of lac-Z reporter genes. These flies will be crossed to flies mutant for candidate regulatory genes. This work should fill the large gap in our knowledge on the genetic mechanisms controlling the Hox genes of both Amphioxus and vertebrates.