The Evolution of Body Plans: A TALE of two proteins

A group of genes known as homeobox (Hox) genes control embryonic development of the body plan in a wide range of animals, from humans and fruit flies to cats to beetles. These disparate animals, like many other familiar creatures, have bilateral symmetry, with similar left and right halves of a body laid out along a head-to-toe axis. During development, this axis is divided into a series of segments, and the Hox genes are well-known for determining what structure form in each segment — that is, they control where the head, shoulders, knees, and toes go; mutations in Hox genes famously results in body parts sprouting in the wrong place. Hox genes are highly conserved; a Hox gene from a chicken can do its job just as well in a fruit fly, even though the two are separated by hundreds of millions of years of evolution.

The Hox genes accomplish their task by activating a cascade of other genes; to do this, they interact with genes from the TALE family. Together, the combined Hox-TALE binds to the DNA of downstream genes and switches them on, setting the development of an antenna or a leg into motion. In a paper appearing in the open-access journal eLife, an international team of researchers has shown that this interaction isn't confined to bilateral animals but also happens in in radially symmetric animals like jellyfish and starfish. This means that this genetic circuit, a critical network in bilaterian development, is actually much older, dating back to at least the split between these two ancient lineages. Based on these findings, the Hox-TALE interaction is an ancient regulatory module common to all Eumetazoa which was later co-opted for anterior-posterior patterning in bilaterians.

To discover this, the researchers looked at the Hox and TALE genes in the tiny starlet sea anemone Nematostella vectensis (pictured above), which has a radially symmetric body plan. They found that genes from the two groups are expressed in the same location in N. vectensis and can form a complex together which then enters the cell's nucleus, just as in bilaterians. Although a Hox-TALE complex formed in radially symmetric animals, the researchers didn't know if it was functionally similar to the one in bilaterally symmetric animals; the Hox-TALE unit could bind to DNA, but what was it doing?

The team took a direct approach to answering this question: test the N. vectensis genes in well-established bilaterian model systems, namely the fruit fly Drosophila melanogaster and the African clawed frog, Xenopus laevis. Despite differences in the genetic sequence, the sea anemone Hox and TALE genes were able to fill in for their Drosophila counterparts in flies lacking those genes, and a mis-expressed N. vectensis gene even turned the fly's antenna into a leg. Likewise, an anemone TALE gene was good enough to activate the expression of several patterning genes in Xenopus embryos. Finally, the researchers included a negative control; TALE genes from the unicellular amoeba Acanthamoeba castellanii weren't able to form a complex with Hox and activate downstream genes. In the authors' words, this work "underlines that the evolution of the TALE partners enabled the interaction network with Hox proteins and hence new functions to emerge during eukaryote evolution."

Reference
Hudry, B et al. Molecular insights into the origin of the Hox-TALE patterning system. eLife 3:e01939. (2014) doi: 10.7554/eLife.01939

Image credits
The Nematostella image is by user Cymothoa exigua via Wikimedia Commons.