Muscle cells crawl across fruit fly organs to build body structures

Organs are not molded like blobs of passive clay. They rise from busy landscapes where cells crawl, tug, and signal until form emerges.

In new work with the humble fruit fly, researchers watched future muscle cells roam across a juvenile testis, squeeze it like a drawstring bag, and twist the tissue into its adult spiral.

What they learned about this roaming workforce may also explain how tumors invade distant sites.

Dr. Maik Bischoff of the University of North Carolina at Chapel Hill, together with colleagues in the Peifer Laboratory, led the project and captured the shape‑shifting drama in living animals.

Fruit fly organs shaped by muscle cells

The fruit fly Drosophila melanogaster starts with a smooth, oval testis. Within hours, waves of mesenchymal cells – motile precursors that resemble fibroblasts – glide over its surface.

These cells do not travel at random; they move as a sheet in a process known as collective cell migration. Coordination keeps gaps from forming and ensures every patch of the organ gets covered.

Most textbooks credit nearby epithelial cells with the heavy lifting of organ building, because epithelial sheets act like bricks and mortar.

The new study shows that migratory peers can be just as important, especially when an organ must change length, curvature, or torsion.

Each precursor advances roughly one body length every ten minutes, a pace that, scaled to human size, would equal a jog along a football field every hour.

Cells crawl to shape the fruit fly testis

“Trying to figure it out from static images is like learning the rules of basketball from a handful of screenshots,” said Bischoff. His team labeled the precursors with fluorescent markers and filmed them for six hours.

The videos of fruit fly organs forming revealed alternating bouts of advance and constriction: cells first crawled distally, then tightened the actin belt wrapped around the testis.

To capture these speeds, the team used a spinning‑disk microscope paired with adaptive optics that collected volumetric stacks every 30 seconds without bleaching the tissue.

The group found that each precursor keeps at least three filopodia in contact with its neighbors, acting like fingers in a zip‑lock seam. When one cell stalled, the seam held firm and force propagated through the sheet, much like hikers roped together on ice.

The choreography echoed computer models showing that follower‑guided migration remains robust even when leaders falter.

Fruit fly organs and nerve signals

Unexpectedly, the roving precursors spoke in the chemical language best known from neural development. The key messenger is semaphorin, and its receptor plexin sits in the cell membrane acting as a brake and steering wheel at the same time.

Biochemists often study the pair for their role in guiding axons, but the same duo now turns up in gonad shaping.

Genetic tricks showed that reducing plexin made testis‑wrapping cells clump together, while too much plexin caused them to drift apart. Either imbalance opened holes in the muscle coat.

The effect mirrors work in vertebrates where semaphorin‑plexin circuits can either loosen or tighten junctions depending on context.

From fruit flies to mammals

Intriguingly, fruit‑fly semaphorin‑1b seems to temper plexin rather than activate it, an antagonism that is echoed in mammalian semaphorin‑6A that fine‑tunes cortical neuron spacing.

Downstream of plexin, the small GTPase R‑Ras2 flips between on and off states to regulate integrin‑mediated grip on the underlying matrix, a mechanism previously linked to blood vessel stability.

The fruit‑fly result hints that the same switchboard may tune adhesion in very different tissues.

How cancer cells move

Cancer cells hijack developmental playbooks when they leave a primary tumor. They often assume a mesenchymal identity, migrate collectively, and “talk” through semaphorin‑plexin signals that were turned down after birth.

A 2024 review cataloged over a dozen tumors in which plexin signaling correlated with invasion depth and metastatic load.

“Mesenchymal cells are often overlooked in organ development, but they’re incredibly dynamic and influential,” noted senior author Dr. Mark Peifer.

Because the fly testis is easy to image and manipulate, it offers a rare window into how normal migratory sheets avoid tearing. Tumor clusters face the same engineering problem when they travel through cramped extracellular spaces. 

The team’s discovery that a neuron‑style guidance cue balances cohesion and flexibility could explain why blocking specific semaphorins slows breast cancer spread in mice.

If the pathway keeps malignant cells together, disrupting it might splinter a cluster into cells too weak to survive alone.

Fruit flies and organ development

Beyond oncology, insights from fruit flies add a control knob for future tissue‑engineering projects. Synthetic organoids usually rely on patterned growth factors and stiff scaffolds, yet they still collapse or fold unpredictably.

Tuning semaphorin or plexin activity could let bioengineers guide cell streams to carve channels, chambers, or helical shells without external molds.

Pharmaceutical firms already test small‑molecule plexin inhibitors for neuropathic pain; the same toolbox now has potential in regenerative medicine if dosing can be localized.

The approach may also help repair injuries in adults. Endothelial sheets that line blood vessels regenerate by collective migration, and aberrant R‑Ras signaling is tied to leaky capillaries in diabetes.

Insights from fruit fly organ development could point to drug targets that restore vessel integrity after trauma or stroke.

Building transplant-ready tissues

Finally, Bischoff’s high‑speed imaging of fruit flies, which records thousands of cell paths in deep tissue, sets a new standard for studying morphogenesis.

Combining it with optogenetic switches that toggle plexin within seconds might reveal how transient pulses of adhesion control long‑term shape.

Such precision will be essential for building transplant‑ready tissues where every curve counts.

The study is published in the journal Science Advances.

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