Fruit fly model identifies key regulators behind organ development

Jeremiah Zartman holds a sample of fruit flies in his lab.

A new computational model simulating fruit fly wing development has enabled researchers to identify previously hidden mechanisms behind organ generation.

Since organs develop in remarkably similar ways in fruit flies and people, biological insights from this model can be used to inform the diagnosis and treatment of human diseases, such as cancer, Alzheimer’s and congenital genetic birth defects.

Jeremiah Zartman, a bioengineer and associate professor of chemical and biomolecular engineering at the University of Notre Dame, together with a multidisciplinary research team that includes collaborators from the University of California Riverside, has developed a fruit fly model to reverse engineer the mechanisms that generate organ tissue.

Their findings, which offer a deeper understanding of the chemical and mechanical levers regulating organ cell size and shape, have been published in Nature Communications.

Jeremiah Zartman
Jeremiah Zartman, a bioengineer and associate professor of chemical and biomolecular engineering at the University of Notre Dame

“We’re trying to simulate an organ in the computer—effectively creating a digital twin of that organ,” said Zartman. “We’re taking the different cells and parts of cells to see if we can predict how they will interact with each other.”

Organs develop in response to what Zartman calls a “symphony” of signals. Their fruit fly model integrates the numerous signals that orchestrate cell movement, contraction, adhesion, and proliferation. It also incorporates the mechanical, chemical, and structural properties of cell components and accounts for how these properties change over time and in different locations.

Both the model and his lab’s experimental results showed that there were two distinct classes of chemical signaling pathways, or sequences of signals, that produce either curved or flat tissues—identifying the flexibility and tunability of generating an organ of a specified shape.

A graphic from Zartman's paper showing the curved versus flat nature of the fruit fly wing.
Different chemical signaling pathways produce either curved or flat tissues

Cells receiving signals from insulin led to an increase in the curvature of the tissue, while cells receiving inputs from other key growth regulators (Dpp and Myc) flattened tissue. The researchers discovered that these growth regulators also manipulated the cell’s internal framework, or cytoskeleton, to further sculpt cell size and shape. 

The Zartman group’s big-picture goal is to identify the extent to which the biological rules gleaned from simulated fly organ studies are shared with systems as distinct as plants, fish and humans.

“Our goal for the future is to develop a digital prototype organ that tackles a fundamental question in biology—how do cells generate functional organs?” said Zartman. 

A closeup of a hand holding a sample of fruit flies in a tube
Fruit flies and fruit fly larvae

The team’s ongoing work is funded by NSF’s Emergent Mechanisms in Biology of Robustness, Integration & Organization (EMBRIO) Institute as well as the Models for Uncovering Rules and Unexpected Phenomena in Biological Systems (MODULUS) program.

— Karla Cruise, Notre Dame Engineering; Photos by Wes Evard, Notre Dame Engineering