Research into fruit fly wings provides a peek into birth defects

How a developing organ robustly coordinates cellular mechanics and growth must be understood to reach a final size and shape. A new study from UCR sheds light on how fly embryo cells develop as required.

The study reveals insights into human development and possible treatments for congenital disabilities.

Instead of investigating tissue development, scientists in this study used some of the most powerful supercomputers in California to simulate many cells working together.

The group examined the cells’ elasticity and fluid pressure, as well as other mechanical characteristics. Additionally, they examined the process by which a “wing disc,” or collection of many cell types, divides to form wing tissue.

Mark Alber, UCR distinguished mathematics professor and senior co-author of the study, said, “We modeled hundreds of cells, trying to figure out how they interact with each other, in this case, to become the wing of a fruit fly.”

Working with quantitative biologists and bioengineers from the University of Notre Dame, scientists observed that the wing disc is evenly bent in the early stages of development. However, the bottom flattens while the top maintains its curvature in later phases. 

From a cross-sectional perspective, the disc starts flat and gradually takes on the appearance of a rainbow. Scientists eventually have a top and bottom that no longer mirror each other because the top maintains its shape while the center bottom flattens.

Jennifer Rangel Ambriz, UCR mathematics doctoral student and paper co-first author, said, “We wanted to understand what causes this shape because the flies won’t fly or survive if development doesn’t happen properly.”

The team discovered that actomyosin, a subcellular component, is primarily responsible for the flattening of the lower wing disc during development. The actin fiber network that makes up this structure is dynamic and influences the height and stiffness of the cells.

Actomyosin pulls the nuclei of specific cells back and forth during cell division and expansion to alter the geometries of the individual cells that comprise the wing disc.

“For a cell to divide, the nucleus has to move into the top region of a cell, and it does so based on the actomyosin network,” Rangel Ambriz said. “It’s like a fist on a tube of toothpaste. When you squeeze the bottom, it moves everything to the top.”

Additionally, actomyosin connects with the collagen-based extracellular matrix, or ECM, which is a crucial component. The extracellular matrix (ECM) holds the cells in the wing disc together and prevents them from moving too far apart, especially during cell division. The ECM’s relative stiffness or flexibility has a significant impact on the growth and form of tissues.

In the future, scientists want to learn more about the chemical and genetic cues that influence actomyosin. Different chemical signals probably play a major role in shaping tissue shape, even though mechanical elements like pressure and membrane surface tension in the cells also impact it. 

“In the embryo, if you cut a cell or even several cells, the tissue still develops as it should,” Alber said. “What we know now about factors that affect tissue development could have applications beyond fruit flies and might enable tissue regeneration in humans or animals.”

The group also hopes that their research will help rectify flaws in human tissue development. 

Scientists could use these fly models to relate genes that control the development of tissues to certain situations, identify genes responsible for specific birth defects, and modify or rectify these genes over time.

Journal Reference:

Kumar, N., Rangel Ambriz, J., Tsai, K. et al. Balancing competing effects of tissue growth and cytoskeletal regulation during Drosophila wing disc development. Nat Commun 15, 2477 (2024). DOI: 10.1038/s41467-024-46698-7

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