Natural variation of embryo development across the insect order of flies

Our long-term goal is to understand how embryos evolve. Many developmental mechanisms are similar between species as different as humans and flies, but occasionally they differ strikingly even between closely related species. Explaining such unexpected plasticity in developmental gene networks will help us understand the basic science of developmental robustness and congenital disease in all animals, including humans. Comparing multiple closely related species is a powerful approach for understanding causes of plasticity in gene networks but is extremely difficult to implement with vertebrates. However, it can be accomplished with flies (Diptera) because many fly species are readily cultured at low cost and are amenable to functional studies. Moreover, a leading genetic model organisms in developmental biology, the fruit fly Drosophila melanogaster, can serve as entry point for comparative functional studies. We therefore established experimental tools and genomic resources for a set of non-traditional dipteran model organisms to study how developmental mechanisms change and diversify in the course of evolution. We discovered that different fly species use unrelated anterior determinants (ADs) to establish the anterior-posterior (AP) axis of the embryo. While Drosophila’s AD (Bicoid) is a widely studied morphogen model, lower dipterans use a range of unrelated transcription factor encoding AD genes. Our recent research shows that ADs of two lower dipteran species, the moth fly Clogmia albipunctata and the harlequin fly Chironomus riparius, differ in their target genes and mechanisms of action (e.g., activation versus repression). This discovery was possible after generating genomic resources for our model organisms and combining knowledge of DNA-binding motifs of the disparate ADs with quantitative measurements of chromatin accessibility and gene expression in precisely staged single embryos with normal or reduced AD activity. We also obtained preliminary evidence that the mechanisms for initiating axial symmetry-breaking in higher dipterans (Brachycera), such as the soldier fly Hermetia illucens, a close outgroup to the clade of species in which bicoid occurs, or the flesh fly Sarcophaga bullata which lost bicoid, differ more radically. It is not known to what extent the segmentation gene networks differ between dipterans and how they converge during embryogenesis to establish the conserved segmented body plan. We will use these and additional species as entry points to examine through the expanded use of scalable (epi-)genomic approaches and functional experiments in vivo (1) how dipterans diversified their segmentation gene networks in evolution while converging in development on a segmented body plan and (2) how and why molecular mechanisms of axial symmetry breaking diverged. Answers to these questions will help to explain how, when, and why developmental gene networks of embryos reorganize. Project Number: 1R35GM161741-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: URS Schmidt-Ott | Institution: UNIVERSITY OF CHICAGO, CHICAGO, IL | Award Amount: $480,083 | Activity Code: R35 | Study Section: Special Emphasis Panel[ZRG1 CDB-E (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11260788