Our group uses Drosophila melanogaster to understand how JAK/STAT signalling and Hox proteins activate the complex gene networks inducing the development of various organs. We are especially interested in finding out how these organogenetic networks may have evolved. To this end we are analysing the surprisingly similar gene networks specifying the formation of five very different organs: the endocrine glands controlling insect moulting and metamorphosis (the corpora allata and the prothoracic glands), the respiratory organs (the trachea and the posterior spiracles), and the testis. We have evidence showing that the comparative study of the gene networks activated in these five specialised organs can help to understand the evolution of gene networks by divergence and by co-option.
1- Gene network divergence during the evolution of homologous organs:
Despite their different shape and function, we have developmental and genetic evidence indicating that endocrine glands and trachea evolved by the divergence of an ancient metamerically repeated organ. We have found that the trachea, the corpora allata and the prothoracic glands form at segmentally homologous positions, they can be homeotically transformed into each other, and they are specified using very similar gene networks involving JAK/STAT signalling and Hox input. However, despite their homology, the glands and the trachea primordia have different developmental behaviours that are mediated by the differential activation in the glands of the Sna epithelial to mesenchymal transition (EMT) regulator and by the activation in the trachea of the Trh transcription factor. We have also found that a conserved insect endoskeletal element, the tentorium, originates in the head from this same homology group of cells. We are currently analysing the genes shared by these three organogenetic networks, as well as the organ specific genes whose activation leads to their developmental diversification.
2- Co-option of the posterior spiracle gene network:
We found that Abd-B modulates in the eighth abdominal segment (A8) a gene network that includes several signalling pathways and other transcription factors, which activate cell adhesion proteins, cell polarity regulators and cytoskeletal regulators.
Our analysis of this posterior spiracle gene network uncovered an evolutionary novelty, the activation of the posterior-specific engrailed gene in the anterior part of the A8 segment. Engrailed expression has been restricted over 500 million years to the posterior part of each segment in all arthropods. Comparison of En expression in other Diptera shows that the anterior A8 compartment activation evolved in the Drosophilids. Using CRISPR/Cas9 we have deleted the enhancer driving the anterior spiracle specific A8 en expression. Despite eliminating En expression from the A8 anterior compartment, the deletion does not result in abnormal spiracle organogenesis, but males are sterile. We have found that Engrailed and the en spiracle enhancer are expressed in the mesodermal cyst cells that encapsulate the sperms in the adult testis, where they are necessary for sperm liberation (spermiation). We discovered that a substantial part of the posterior spiracle gene network is activated in the testis cyst cells using the enhancers driving expression in the embryonic spiracles, suggesting that the posterior spiracle network has been recently co-opted to the testis. We are currently analysing what is the role of the posterior spiracle genes in the testis and how this co-option event has affected the posterior spiracle regulatory network.