How bats became the only flying mammals
Bats stand apart as the only mammals capable of true powered flight. Their secret isn’t a radical new genome, but a smart reapplication of old genetic tools. Scientists have long wondered how a five-fingered limb could morph into a wing with a delicate skin sheet. A recent study published in Nature Ecology & Evolution tracks how regulatory evolution—how, when, and where genes are turned on—shaped this remarkable transformation.
From the outset, researchers expected dramatic genetic differences to underlie such a leap. Yet, as more mammalian genomes were compared and embryonic development observed, it became clear that most genes are shared across mammals. What changes is not the gene list but how those genes are deployed during limb formation. The big question became: how can the same blueprint produce such different outcomes?
The chiropatagium mystery and a nuanced answer
In bats, the forelimbs stretch to form the wing primarily through the chiropatagium, a thin membrane spanning the digits. Traditional thinking suggested that bats retained wing skin by suppressing interdigital cell death (apoptosis) during development. If apoptosis is inhibited, the tissue between the fingers would persist, creating a continuous wing surface.
To test this idea, researchers built an “interspecies limb atlas,” profiling more than 180,000 cells from embryonic bat and mouse limbs. They combined single-cell RNA sequencing with other genomic tools to map the major cell populations—bone, muscle, connective tissue, and skin—across critical developmental stages. Surprisingly, at the cellular level, bat and mouse limbs were nearly indistinguishable: the same cell types appear whether the limb becomes a paw or a wing, and the same apoptotic programs operate in both species.
The team then zeroed in on the chiropatagium itself, sequencing cells from that region. They found a specialized population of fibroblasts—connective tissue cells—present only in bat forelimbs between the digits. Rather than inventing a brand-new cell type, evolution repurposed an existing population that sits closer to the shoulder in mice. In bats, these cells reside in the distal limb near the developing digits and carry a distinct genetic identity, driven by two transcription factors: MEIS2 and TBX3.
In most mammals, MEIS2 and TBX3 are silenced before the fingers form. In bats, however, they are reactivated in the wing-forming region, guiding the identity of this fibroblast population and potentially influencing how the tissue between digits is sculpted by apoptosis. This is an example of evolutionary co-option—using established gene programs to build a new structure, rather than creating entirely new genetic modules.
Testing the idea in mice
To determine if these regulators could drive wing-like changes, the researchers engineered mice to express bat versions of MEIS2 and TBX3 in the developing distal limb and interdigital tissues. They used an enhancer to activate these genes in the fingers and the webbing between them. The results were striking: mouse embryos grew webbed digits, and the tissue between the fingers thickened and organized into a more bat-like wing region. Some cells in the webbing adopted gene expression patterns found in bat wing fibroblasts, and the limb showed tangible, three-dimensional differences, including fused digits and expanded connective tissue.
“With just these two transcription factors, we could partially recapitulate the bat’s wing-building program,” said one of the study’s authors. It’s important to note that turning a mouse into a bat is far from complete flight—flight requires coordinated shifts in bones, muscles, skin, and more. Still, the work demonstrates the power of regulatory shifts in evolutionary development.
Implications beyond bats
The findings have broader relevance. They hint that other evolutionary innovations—bird wings, fish fins, whale flippers—may arise through similar regulatory tweaks using existing gene networks. Beyond evolutionary biology, understanding how digit separation and tissue patterning are controlled could illuminate human developmental disorders, such as syndactyly, where fingers remain fused. Deciphering which genes influence digit separation may improve diagnosis or open avenues for treatment.
As researchers continue applying single-cell technologies to development, they expect to uncover more cases where evolution repurposes old genes in novel contexts. The bat study thus underscores a powerful theme: major structural innovations often arise from flexible gene regulation rather than brand-new genetic material.
