Lab rats with wings: The development, genetics and evolution of bat wings
Life on earth is dazzling in its diversity. There are millions of species, each one having its own biological particularities for scientists to discover. Despite the massive array of species that can be studied, some fields, such as developmental and molecular biology, have focused on studying only a small number of species. Many species are too difficult to raise, or mature too slowly to be useful. Since studying the true diversity of biological life is impossible, these scientists attempt to generalize the findings from simple species, such as E-coli bacteria, or lab mice, to more complex species. This effort has been wildly successful, and we have been able to discover many biological concepts that are true throughout all life on earth. The discovery of cells, DNA, and the genetic code all make clear the usefulness of model organisms for discovering traits that unify many organisms, but can they also be useful for researching traits that are unique to a specific, poorly studied group? Recent research seems to show that they are. For instance, we have begun to gain an understanding of how a unique feature, the wing of a bat, develops and evolved. This has been possible because of our understanding of the genetics and development of a model organism, the common lab mouse, Mus musculus.
Bats, the order Chiroptera, are one of the most specious groups of mammals. One out of every five mammal species is a bat. Bats have been able to flourish in a number of ecological roles, with different species feeding on fruit, insects, fish and perhaps most famously, blood. The reason for this spectacular diversity is the bat’s ability to fly. Once early bats had evolved the ability to fly, numerous ecological niches opened up to them, and many species were able to diverge in a relatively short period of geological time. This is an evolutionary phenomenon called “adaptive radiation”. However, due to the speed of these adaptive radiation events, they leave few traces in the paleontological record. In the case of bats, all recognizable fossils already have the hallmark elongated flingers, which would have supported wings capable of flight. Since we cannot discover clues to bat evolution from fossils, we have to look in other places. Development and genetics have been able to shed considerable light on evolutionary change, but the genetics of bats has not been thoroughly examined. Thankfully, discoveries in model organisms, such as mice, have made clear the developmental and genetic changes that have occurred during bat evolution to allow the formation of wings. Two of the most important and best studied of these changes are the elongation of the finger bones and the appearance of webbing between those fingers.
Embryological studies of model organisms, such as mice, have revealed that the limbs of most vertebrates have webbed digits in early development. Later on, molecular signals in the embryo instruct the cells that make up the webbing to undergo programmed cell death. The molecule that creates this signal, called bone morphogenetic protein (BPM), has been identified in mice and other model organisms. How do bats evade the action of BMP to maintain their primordial webbing? Again the first clues were found in animals that are far easier to study than bats: ducks. Ducks are domesticated and lay eggs that can easily examined for developmental research, but they also produce membranous webbing between their toes. Research showed that they produced BMP just like mice did, but were suppressing its action. That suppression was due to the production
of a molecule called GREMLIN, that interacts antagonistically with BMP. By producing GREMLIN, ducks were blocking BMP from communicating with any cells, allowing the webbing between the toes to evade destruction and appear in the adult. Could bats be using a similar method to maintain the webbing in their wings? This seems to be the case. Once developmental research was conducted, it was found that although bats produce BMP, they also produce GREMLIN, blocking its action. However, the story is more complex than that. Experimentally raising the dosage of BMP, so that it could not be completely blocked by GREMLIN, did not degrade the bat’s wing membranes. Some other factor was helping GREMLIN maintain the initial webbed state of the digits. Thankfully, due to careful work in model organisms, there have been numerous molecules identified that reduce the likelihood that cells will undergo the planned self destruction that BMP causes. One group of these molecules, fibroblast growth factors (FGFs) are abundant in the developing tissues that will become a bat’s wing membrane. When scientists reduced the amount of FGFs, and increased the amount of BMP, the affected bat wings were significantly reduced. It now seems as though those two molecules, GREMLIN and FGFs, are responsible for the membranes that have allowed bats to evolve the ability to fly. Work conducted in model organisms was able to shed light on an evolutionary novelty and identify the changes that might have taken place genetically during bat evolution.
But bat evolution is characterized by more than webbed fingers. For that webbing to become a wing, the fingers themselves must grow significantly. Once again, research conducted in model organisms can help illuminate how these changes take place. The development of limbs has been very closely studied in mice and other model
vertebrates. Each limb begins as a bulge of cells protruding from the body. These cells then divide, with some cells forming central cartilage based struts, which lay out the framework for future bones. When the development of bat embryos is observed, the pattern is initially similar. The limb bud and early wings of bat embryos look similar to the corresponding stages of mouse arm development. But before the cartilage struts give way to bone, differences begin to appear. The cartilage struts spend a much longer time dividing and growing before they finally turn into bone, and the fingers therefore become much longer. How do these differences in development arise? The answer once again was found due to our understanding of mouse development. In mice, the growth of the cartilage struts is controlled by a molecule that we have already become familiarized with, BMP. The role that this molecule plays in limb development was worked out by experimentally modifying the levels of BMP in the limbs of developing mice. The mice that were exposed to high levels of BMP grew particularly long fingers, and the cartilage struts that they formed during development grew for a longer period of time before becoming bone. To put it another way, mice limbs that are grown in high BMP environments develop in a way that is similar to normal bat limb development. These findings seem to suggest that the elongated fingers of bats could be due to higher levels of BMP. This idea is supported by research that shows that bats do in fact produce high levels of BMP in their developing limbs.
But BMP is not the only molecule that might be implicated in the elongation of bat limbs. In fact, there are many genes that are suspected to impact this process, and not all of them are as well understood as BMP. Thankfully, even when the specific functions of these genes are not well understood, model organisms allow us to determine how these
genes might be implicated in bat evolution. For instance, one gene, Prx1, was implicated in limb elongation because mice that were missing the gene had very small, shortened limbs. To assess whether this gene was more active in bats than mice, scientists simply removed part of the mouse genome that controls how active Prx1 is, and replaced it with the corresponding portion of the bat genome. In these transgenic mice, the limbs developed in a way that was slightly similar to bat development, with a resulting limb that was a little bit longer. Because of work in model organisms, biologists can identify the small genetic changes such as these that were likely important during bat evolution.
Despite the lack of fossil evidence, a picture is beginning to emerge of how bats might have evolved. This picture is based on developmental and genetic evidence, despite the fact that very little genetic work has been done in bats. This problem is bypassed because of the utility of model organisms. Animals that are easy to raise and develop quickly, such as mice, have been studied in great detail, and the insights from that research can be used to shed light on novelties in other species, such as bats. For many decades, scientists have been able to use model organisms to discover traits that are universal to all life on earth. Because of this, the biologist Jacques Monod once famously quipped that: “What is true for E. coli is true for the elephant.” But the way in which model organisms have proven useful in studying evolutionary novelties demands a new slogan: “what is unique in the elephant is explained by E. coli.”
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