New Limbs from Old Fins, Part 3: Homology
In the previous posts, we saw that the remarkable blueprint that underlies all limbs – one bone, two bones, blobs, digits – has deep roots in the fossil record. And we looked at fossil intermediates that strongly suggest that the limb pattern was originally constructed in fish fins. It seems that fish fins were modified to produce tetrapod limbs.
The fossil data paint a picture of common descent: animal limbs are descended from fish because tetrapods are descended from fish. This means that, in some sense, a limb is a fin or, more specifically, a modified fin. It's not enough to say that fins and limbs are similar, or that they are constructed using similar principles of design. They are linked by descent, similar to the way an adult human is linked to the amorphous embryo that attached to her mother's womb decades before.
Homology: historical continuity between fins and limbs
In biology, there is a specific term for this kind of relationship. It's called homology. Two structures are said to be homologous if they are both descended from the same ancestral structure. The key criterion is not structural or even functional similarity, although both may apply to a pair of structures of interest. The key criterion is historical continuity. When a biologist says that a bat wing is homologous to a mouse limb, she is saying that both are modified descendants from the same common ancestor.
So, for example, the head of a bat is considered to be homologous to the head of a rat. More interestingly, the wing of a chicken is considered to be homologous to the arm of a monkey or the front flipper of a walrus. Wings and arms and flippers are obviously diverse in their functions and appearance, but all are considered homologues.
Looking at embryonic development of fins and limbs
By contrast, consider the famous panda's thumb (marked “rs” in the image below): it looks like a thumb and acts like a thumb, but it's not homologous to the human digit that makes our hands so useful. The panda's thumb is an enlarged carpal bone, and not a true digit at all. It's a false thumb.
The example of the panda's thumb raises an interesting question. How might we determine whether two biological features are homologous? We can look at fossils, to see if we can trace the development of each feature back to a common ancestor. And that might help a lot. Or we can look carefully at the structure of each contestant, to see if they are as closely related as a more superficial examination might have suggested. But here's another strategy: we can trace the development of each feature during the life history of the animal. In other words, we can see if the two features have similar – or identical – embryological origins. Such a strategy can be decisively informative. In the case of the panda's thumb, a quick glance at the anatomy of the thing shows it to be not very thumb-like, and the clincher comes when we watch (or infer) how it grew. That process is utterly un-thumb-like.
A look at the structure of a chicken wing suggests that it's homologous to a walrus flipper – they both display the telltale blueprint despite their striking differences in outward appearance and function. But the hypothesis would be significantly strengthened if we found that both structures developed in the same way.
When we compare the embryonic development of fish fins and tetrapod limbs, we see remarkable evidence of homology. In this post, we'll look at how the cells that make a limb or fin signal to each other. In the next post, we'll look “under the hood” at the genes that control the process.
Embryonic development of limbs – in the chick
The chick has long been a favored system in which to study embryonic development. The process is accessible and easy to manipulate, and almost two centuries of ongoing work has generated a vast storehouse of basic knowledge. Until relatively recently, when the mouse became a dominant experimental system, almost everything we knew about the development of vertebrates came from studies of chicks. Extensive studies of chick embryos yielded a basic outline of the development of limbs that goes as follows.
At a particular position in the early embryo, at a stage at which the embryo looks vaguely like a worm, a chemical signal is sparked and begins to tell the cells in the vicinity to divide. The chemical is a protein called Fibroblast Growth Factor-10, or FGF-10.
As a result of that signal and the cell division it triggers, a bulge appears on the side of the embryo. It's called a limb bud. The edge of the limb bud starts to make another FGF (FGF-8), and that signal tells the cells inside the bud to keep dividing. The bud continues to grow.
The FGF-8 signal also tells the back part of the limb bud, but not the front part, to start making a special chemical messenger. That messenger is a protein called Sonic Hedgehog (SHH). This region of the limb bud is so important that it has its own name: the zone of polarizing activity, or ZPA. As you might guess, the ZPA functions to polarize the limb. Specifically, the ZPA causes the limb to have a front and a back, and SHH is the chemical message that accomplishes this.
The SHH protein from the ZPA region stimulates the edge of the limb bud to become a special region called the apical epidermal ridge (the AER). The AER pumps out the proteins FGF-4 and FGF-8, which further stimulate the ZPA to ooze out SHH. It's an auto-activating loop: SHH protein causes the ridge (the AER) to make more FGF proteins, which cause the ZPA region to make more SHH protein. In the chick embryo pictured on the right, the dark purple arc-shaped strips are the sites of FGF-8 production in the AER, which is the edge of the paddle-shaped limb buds.
If that was a bit too much jargon for you, here's a simplified version. A chemical signal, A, starts a the growth of a simple primordial limb bud. That signal also turns on a secondary signal, B, which causes the bud to grow more and which activates a localized signal, C. That localized signal will help the bud to have a front and a back, and that signal also turns on a self-reinforcing loop between C and another signal, D. That loop makes the limb grow.
Embryonic development of limbs – in the mouse
That's how it works in the chick. When mouse genetics got big in the last two decades, biologists began analyzing the processes that control mouse development, using tools for genetic manipulation that chick developmental biologists could only dream about. You can probably guess what they found. The process is the same. The same FGFs act to induce the same SHH signal in a ZPA with the same characteristics. That ZPA induces the same FGF/SHH signaling loop.
What do we mean when we say that these systems are the same? Well, for one thing, the protein signals are highly similar to each other, suggesting that they are homologous. Furthermore, the signals are functionally interchangeable between different organisms. Amazingly, the SHH from a chicken can support development in a fly, substituting for a protein called Hedgehog that is thought to be a distant homologue of SHH. And finally, an extraordinary experiment in 1976 showed that the ZPA from a mouse can induce limb development in a chick. Think about it: the core developmental processes that make wings and arms are the same.
Embryonic development of fins
So what about fish fins? If chick wings and fish fins are homologous, we should expect to see substantial overlap in these developmental systems. And, remarkably, that's what we see. FGF-10 gets things started, then FGF-8, SHH, and FGF-4 interact to keep things going. When FGF-10 is deleted from a mouse, you get a limbless mouse. When FGF-10 is damaged in a zebrafish, you get a finless zebrafish. (Both are pictured below.) What does SHH do in a zebrafish fin bud? Same thing it does in a mouse limb bud. The commonalities in the basic system are strong enough that one recent research report on the effects of FGFs in zebrafish discussed limb buds and fin development interchangeably.
Developmental systems are the same in chick, mouse, and fish
These striking facts about vertebrate development are elegantly explained by common ancestry. The basic systems, established hundreds of millions of years ago, can be tweaked to get slightly (or significantly) different outcomes. The tetrapod blueprint – one bone, two bones, blobs, digits – is largely the same in diverse tetrapods because the developmental systems that make the limb are largely the same. And the roots of the system go all the way to ancient fish, whose fins contained similar structures that seem to have been built by core developmental systems maintained in both fish and tetrapods to this day.
How do we explain all this?
It seems to me that design is much less effective as an explanation for the apparent homology between fin development mechanisms and limb development mechanisms. Take the FGFs, for example. There are several other families of protein growth factors in animals, and there may be zillions of other ways to make a protein signal besides the small number of ways that we see in nature. And yet we see the same particular proteins used for these signaling purposes, over and over, in organisms as distinct as fish, chickens, and mice. Why is it that FGFs must be used for the purpose of directing the formation of a limb bud? Why are specific FGFs used for these purposes, when experiments show that the different FGFs (e.g., FGF-10 and FGF-4) are often interchangeable? Are these commonalities indicative of a design constraint, or do they represent the preferences of the designer? Without addressing such serious questions, we can't establish design as a competing explanation. If limb and fin development couldn't have been designed otherwise, then we should try to find out why. And if they could have been designed in myriad different ways (as I believe they could), then we should try to find out why things went the way they did. Modification from a common ancestor provides a coherent explanation, even when the developmental facts are considered alone. Add the fossil record, and I hope you can see that the explanatory power of common descent is impressive indeed.
In the next post we'll look again at fin and limb development, this time focusing on the genes that set up the patterns. As before, we'll discover a striking pattern of homology.
Neil Shubin (2009) Your Inner Fish: A Journey Into the 3.5-Billion-Year History of the Human Body. New York: Vintage Books.
Brian K. Hall, editor (2007) Fins into Limbs. Chicago: The University of Chicago Press.
Scott F. Gilbert (2000) “Chapter 16. Development of the Tetrapod Limb.” In Developmental Biology, 6th Edition. Sunderland (MA): Sinauer Associates.
John Gerhart and Marc Kirschner (1997) Cells, Embryos, and Evolution. Malden (MA): Blackwell Scientific.
Panda's false thumb is from Figure 1B of Salesa et al. (2005) Proc. Natl. Acad. Sci. USA 103:379-382.
Chick embryo is from Wellcome Images, Creative Commons license.
Mouse embryos are from Figure 2B of Min et al. (1998) Genes & Dev. 12:3156-3161.
Zebrafish embryos are from Figure 1 of Norton et al. (2005) Development 132:4963-4973.