# Genetic variation and function of body axis determinants in midges and other flies

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $436,396

## Abstract

PROJECT SUMMARY
Our goal is to discover how closely related species adopted unrelated axis determinants for specifying the
anterior embryo. Many aspects of animal development are conserved between species as different as humans
and flies, but some key regulators change very rapidly over the course of evolution for unknown reasons.
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. This
approach is extremely difficult to implement with vertebrate model organisms but can be readily accomplished
in insects. Flies (Diptera) are particularly suitable because they include Drosophila melanogaster, one of the
leading model organisms in developmental biology, and because other dipteran species that can be cultured in
a laboratory setting are amenable to functional studies. Our research in a variety of dipteran model organisms
during the previous funding period established that these closely related species use a broad range of anterior
determinants (ADs) for establishing embryo polarity and anterior-specific gene expression, most likely through
the formation of long-range transcription factor gradients with morphogen-like activity. This discovery enables us
to examine why key developmental regulators can be highly unstable in evolution.
 While Drosophila’s AD (Bicoid) is a classic morphogen model, it is not known whether its mechanism of
action can be generalized nor how the evolutionary transition to Bicoid-dependent pattern formation was
achieved. The first of these two questions will be addressed by identifying and characterizing chromatin and
gene targets of the AD in the moth fly Clogmia albipunctata, Cal-Opamat (Aim 1) and of the AD in the
common midge Chironomus riparius, Panish (Aim 2). This will be done by testing for AD-dependent
chromatin accessibility in stage-matched embryos with or without reduced AD activity, using ATAC-seq and
RNAi. These experiments will be complemented as needed by ChIP-seq, and by characterizing the expression
and function of predicted target genes in vivo. The second question, concerning the transition to Bicoid-
dependent pattern formation, will be addressed by determining the mechanism of anterior specification in
the soldier fly Hermetia illucens (Aim 3). This organism was chosen because it is the closest tractable
outgroup to the clade of species with bicoid. A pilot study revealed several AD candidates, including Hil-Stau,
the ortholog of Staufen. This RNA-binding protein binds bicoid mRNA in early Drosophila embryos. To identify
Hermetia’s AD, anterior-localized and Hil-Stau-binding mRNAs will be determined by expression studies, co-
immunoprecipitation, sequencing, and their function will be examined by RNAi. The determination of the anterior-
speci...

## Key facts

- **NIH application ID:** 10367757
- **Project number:** 2R01GM127366-03A1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** URS C Schmidt-Ott
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $436,396
- **Award type:** 2
- **Project period:** 2018-09-18 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367757

## Citation

> US National Institutes of Health, RePORTER application 10367757, Genetic variation and function of body axis determinants in midges and other flies (2R01GM127366-03A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10367757. Licensed CC0.

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