One of the most important milestones in the early life of an organism is when the embryo breaks symmetry and arranges itself to form the head (anterior) at one end and tail (posterior) at the other end. Scientists have used the common fruit fly (Drosophila melanogaster) for decades as a model species to study the process for forming the anterior-posterior body axis, along with countless other early developmental and genetic processes.
In fruit flies, a gene called bicoid controls this process. This is a unique gene that only exists in some fly species, but in 2019, Urs Schmidt-Ott, PhD, Professor of Organismal Biology and Anatomy at the University of Chicago, and his team discovered three unrelated and more widely conserved genes that adopted the same job in other fly species . This is an extreme example of developmental systems drift—when developmental gene networks diverge while preserving the outcome—in this case, the head-to-tail axis.
Since then, Schmidt-Ott and his lab developed new genetic tools to study these genes in different fly species. They hope to understand whether the genes work like bicoid or have a different mechanism, and how such substitutions affect the embryo's gene network further downstream.
In a new study published recently in PLOS Biology , they examined the mechanism by which a gene called odd-paired establishes the head-to-tail axis in a moth fly, Clogmia albipunctata. Also known as a drain fly, this harmless species can be found hanging around hot, moist environments like sewer drains, plant pots, or stuffy public restrooms in the summer. To better handle their muggy habitats, they have a dense coat of hair that makes them look like little moths, hiding the fact that they hold keys for understanding how new axis determinants, acting like the well-known bicoid gene, emerged in the course of evolution.
"We knew that the majority of flies lack this bicoid gene, although it's super important in Drosophila," Schmidt-Ott said. "That triggered our search for such factors in other fly species. It turns out each of these other species has its own interesting story."
Taken together, these stories reveal the principle of an evolutionary process in which a different version of the same protein produced from a single gene (known as an alternative transcript isoform) is co-opted as a cue for the embryo's developmental gene network.
In both moth fly and fruit fly embryos, expression of the odd-paired gene ensures that the correct number of body segments form as the larval body plan develops. However, moth fly mothers also express odd-paired earlier, during formation of the egg. This transcript provides a nearly identical protein but at a different time and in a different location—the prospective head region of the egg. This localized early activity of odd-paired is what lets it be reused to break axial symmetry in moth flies.
But the researchers also wanted to know how odd-paired functions at the molecular level in moth flies to break the symmetry. The new study provides answers to their questions about its downstream targets, and if they are the same as the targets of bicoid in fruit flies.
Both bicoid and odd-paired affect chromatin accessibility in the genome, which describes how open or closed a region of DNA is inside the cell nucleus. DNA is packaged with associated proteins to form material called chromatin. Open chromatin is loosely packed and more accessible to be expressed and regulated; closed chromatin is tightly packed and less accessible to genetic machinery.
Fruit flies and moth flies both break symmetry by managing chromatin accessibility in regions of the genome that promote the expression of genes required for developing the head, but their target genes differ. While bicoid has dozens of direct target genes (the earliest and best studied is one called hunchback), the odd-paired substitute of moth flies may not target this gene at all. Instead, moth flies start developing the head by activating two different genes called homeobrain and sloppy-paired.
It is still unclear if these two genes are sufficient to break axial symmetry in most fly species, or if the early embryonic gene networks of other flies are far more diverse. If so, researchers hope that comparing the developmental gene networks of many fly species will help to answer questions about which of these genetic network features are most resistant to change, and why.
Schmidt-Ott said the example of axial patterning in fly embryos shows the value of studying multiple species, even when there is such a well-established model as the fruit fly. "One big benefit of going with these multi-species approaches is that you can see how nature solved the same problem in different lineages," he said. "There are 150,000 described fly species out there, and there is a huge variation in how they achieve the same job of establishing head tail polarity of the embryo. By looking into these natural experiments, I think we can better understand principles of how these mechanisms work and change in the course of evolution."
The study, "Asymmetric chromatin accessibility underlies anterior-posterior axis specification in moth fly embryos," was supported by the National Institute of General Medical Sciences of the National Institutes of Health. Additional authors include Ezra E. Amiri, Muzi Li, Ayse Tenger-Trolander, Maxwell Devine, and Koray Kasan from UChicago; Alexander Thomas Julian from the Illinois Institute of Technology; Sheri A. Sanders from the University of Notre Dame; and Shelby A. Blythe from Northwestern University.
