How understanding organ growth in fruit flies sheds light on genetic diseases

Fruit fly on a leaf
A discovery by Rutgers scientists might lead to better methods for diagnosing and treating human genetic diseases that affect organ development. (Botaurus/Wikimedia Commons)

Rutgers University scientists have made a surprising discovery about how wings form in fruit flies, disrupting long-held beliefs related to organ growth. They believe the finding could lead to improved methods for diagnosing and treating human genetic diseases.

Scientists have traditionally assumed that the orientation of dividing cells regulates the shape of a growing fruit fly wing, but the Rutgers scientists found quite the contrary. Instead of being controlled by the sum of each individual cell’s orientation during division, wing development is governed by a bigger cell blueprint that's mediated by tissue-wide stresses, they found. They published their findings in the journal Current Biology.

The Rutgers team set out to get at the root of what causes deformed organs in the human body. To understand how organ shape is determined in multicellular organisms, the researchers probed the wing of the Drosophila fruit fly. They focused in on the orientation of mitotic spindles—the cell structures that form during cell division to separate chromosomes into two separate daughter cells.

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To further examine that mechanism, the team manipulated a protein called mushroom body defect (mud), which plays a role in spindle orientation. To their surprise, flies with mutant mud genes, or no mud genes at all, developed wings that were similar in shape to those of wild-type controls, even though changing the gene did affect spindle orientation.

The authors hope their finding will lead to better understanding of how the normal shape of human organs is determined, which could help in the diagnosis and treatment of genetic diseases that are marked by abnormal organ development.

RELATED: The promise of regenerating tissues and organs from inside the body

Most research focused on misshapen or damaged organs takes a regenerative approach to reinstate normal functioning. For example, scientists at Duke University created artificial heart muscle using pluripotent stem cells. They believe this type of living, beating "patch" can be used to replace damaged heart tissue in patients who have suffered heart attacks.

The Rutgers scientists hope their research in fruit flies will lead to ideas for treatment interventions that could make a difference much earlier in the disease process.

“By identifying genes that influence organ shape, scientists could screen for alterations in those genes before the symptoms of a disease become evident,” the study’s senior author Kenneth Irvine said in a statement. “If a disease is diagnosed before symptoms appear, people might be able to start a treatment plan to ameliorate the symptoms at an earlier stage.”

Irvine and colleagues are still working to figure out the precise mechanism involved in organ development. They are particularly interested in probing a set of genes required for normal organ shape in fruit flies and people.

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