The Mystery of the Flying Mammals
Bats have long fascinated scientists as the only mammals capable of true powered flight. Their wings are not a new limb but a remarkable modification of the familiar five-digit limb layout shared by all mammals. The question has always been: how do bats become flyers when the genetic blueprint is so similar to that of ground-dwelling relatives?
Regulatory Evolution: The Hidden Dial Tuning Development
For years, researchers searched for dramatic DNA differences to explain the bat wing. However, a growing body of work suggests that the major differences often come from regulatory evolution—changing when, where, and how genes are turned on during development rather than altering the genes themselves. In other words, the same toolkit can produce very different outcomes depending on how it is used.
The Chiropatagium: A Wing That Defies a Simple Tale
At the heart of bat flight is the chiropatagium, the membranous skin stretching between the elongated digits that forms most of the wing’s surface. In many mammals, the skin between the fingers is reduced through programmed cell death, or apoptosis, before birth. It has been proposed that bats kept this tissue by suppressing interdigital apoptosis, thus preserving the wing surface. Yet recent findings reveal a more nuanced mechanism.
A Single-Cell Map of Limb Development
Researchers built an interspecies limb atlas, analyzing over 180,000 cells from embryonic limb tissue of bats (Carollia perspicillata) and mice at key developmental stages. Using single-cell RNA sequencing and other genomic tools, they charted every major cell population involved in bone, muscle, connective tissue, and skin formation. The goal was to compare bat and mouse limb development with a statistical lens to identify how the same genes drive different outcomes.
Surprising Cellular Similarities
The team expected bat wings to rely on novel cell types. Instead, they found that, at the cellular level, bat and mouse limbs are nearly identical. The same cell populations arise whether the limb becomes a paw or a wing. Importantly, signals for cell death—such as Aldh1a2 and Bmp2—were active in the interdigital region in both species, indicating apoptosis still occurs in bats. This challenged the idea that wing formation depended on simply blocking cell death.
Co-Opted Fibroblasts: A New Identity for Old Cells
Delving deeper into the chiropatagium region, researchers identified a specialized population of fibroblasts—connective tissue cells—present between the fingers in bats. Rather than inventing a new cell type, evolution repurposed an existing fibroblast population, shifting its deployment to the distal limb near the developing digits. This reconfiguration helps explain how bat wings acquire their unique structure without wholesale cellular innovation.
Key Transcription Factors
These bat-specific fibroblasts show high activity of two transcription factors, MEIS2 and TBX3. In most mammals, these genes are quiet near the fingers, but in bats they reactivate in the distal limb. Researchers connected these factors to the identity of the wing-associated fibroblasts and proposed that they influence how apoptosis is coordinated during digit separation and wing formation.
Testing the Idea: Turning Bat Signals into Mouse Wings
To test causality, the team engineered transgenic mice to express bat versions of MEIS2 and TBX3 in the developing digits and interdigital tissue. They used a DNA enhancer to activate these genes precisely where webbing would form. The result? Mouse embryos developed webbed digits, thicker interdigit tissue, and bat-like gene activity in the wing-related cells. Three-dimensional imaging confirmed physical changes in the hand area consistent with an early wing program.
Implications: A Powerful Demonstration of Evolutionary Co-Option
“With just these two transcription factors, we could partially recapitulate the bat’s wing-building program,” one author noted. This showcases regulatory evolution at work: existing genes are repurposed and redeployed to sculpt new structures. Achieving true flight, of course, involves coordinated changes across bones, muscles, skin, and neural control, but this study marks a crucial mechanistic step in how such complexity can arise from regulatory shifts.
Broader Significance: From Bats to Human Health
Beyond evolutionary biology, the findings offer insights into human developmental disorders. Conditions like syndactyly, where fingers remain fused, might share underlying regulatory mechanisms with bat wing formation. By mapping how specific genes influence digit separation and tissue patterning, scientists can better diagnose or potentially treat related conditions in the future.
Looking Ahead
The study underscores a broader pattern: evolution often tinkers with genetic “dials” rather than rewriting the entire blueprint. As single-cell tools become more powerful, scientists expect to uncover many more examples of how old genes are creatively repurposed to yield new forms—whether wings in bats, fins in fish, or other remarkable anatomical innovations. For now, the bat remains a striking testament to the elegance of regulatory evolution in animal form.
