PvM at the Panda’s Thumb has already written a bit about this issue in the article “Human Gland Probably Evolved From Gills”, but I’m not going to let the fact that I’m late to the party stop me from having fun with it. This is just such a darned pretty story that reveals how deeply vertebrate similarities run, using multiple lines of evidence.
Here’s the start of the situation: fish have a problem. Like most animals, they need to maintain a specific internal salt concentration, but they are immersed in a solution that is much more dilute they they are (for freshwater fish) or much more concentrated (for saltwater fish). To make matters worse, fish have large respiratory membranes, the gills, which expose a huge amount of surface area to the watery medium. Their answer to the problem is to do much of their regulation of various ions at the gill surface, using sensors and salt pumps to constantly work, extracting excess salts from one side and pumping them to the other. Gills are therefore more than just the organ fish use to breathe—it’s also where they regulate salt balance.
Us terrestrial tetrapods have a different problem. We can’t pump salts out of or into the air, so instead we maintain internal stores of salts (calcium, for instance, is packed into bone) and use hormones to regulate them, by telling cells to either sequester the ions, or to release them into the bloodstream. We don’t do this with gills, obviously—instead, we have several glands that monitor and control blood salt levels.
One of the most important sets of glands for this function are the thyroid and parathyroid glands, which regulate calcium ion balance. When the amount of calcium salts dissolved in the blood drops below a certain level, receptors called CasRs (Calcium sensing Receptors) detect the change, and trigger the parathyroid gland to release PTH (Parathyroid Hormone) into the blood, which tells cells in the bone to gnaw away and free up calcium (which can lead to osteoporosis, for instance), and it also signals the kidneys to retain calcium. The thyroid, which I’m not going to say much about, has a complementary role in managing the situation when blood calcium levels are too high.
So fish have gills to regulate calcium, and we have parathyroid/thyroid glands to regulate calcium. Do they have anything else in common? One minor thing seems to be location: gills are in the fish’s ‘neck’, and the parathyroid glands are located at roughly the same place, in your neck—and that’s interestingly coincidental, since there’s no particular need for these glands to be in that particular location. They can do their job just as well anywhere. And they happen to be located in a particularly fascinating place for those of us curious about vertebrate evo-devo; all kinds of action occurs in this pharyngeal region in early development.
For one thing, many features of the face and neck are assembled from those curious and fateful tissues, the branchial arches, well known for their homology with the gill arches of fish. Here’s a diagram of a 5-week-old embryo on the left, with the arches color-coded, and an infant on the right, showing what connective tissues develop from each arch.
The first arch contributes to the jaw, while the second through fourth are going to form various cartilages in the neck—the cartilages near where the thyroid/parathyroid will form. What an interesting coincidence! Could it be that the parathyroid is also derived from a branchial arch, and is therefore homologous with the gills of fish?
One way to find out is to use an early molecular marker. The parathyroid is distinguished by the expression of a unique transcription factor, Gcm-2. Gcm-2 is expressed only in the parathyroid, and is absolutely critical to its formation: knocking out the gene causes the parathyroid to fail to form. Another useful marker is to stain for CasR, the receptor protein, or PTH, the hormone itself. The top row of pictures (A-D) below show that these are effective markers for the thyroid gland in an older chick embryo. The lower series (E-I) are in younger embryos, at a stage when they have clear pharyngeal arches, stained with Gcm-2.
What you see is that this marker appears early in the third and fourth pharyngeal arches, showing that the parathyroid is derived from the same tissues as fish gills.
This is cool enough, but Okabe and Graham take it a step further. Gcm-2 is a marker for the parathyroid in tetrapods. Fish lack a parathryoid gland, but is Gcm-2 expressed anywhere in them? I think you can guess where Gcm-2 is expressed in fish:
These photographs show where Gcm-2 is expressed in zebrafish and dogfish embryos: the pharyngeal arches! These are beautifully symmetrical results showing that the tetrapod parathyroid is derived from the pharyngeal arches, and that the pharyngeal arches of fish also express a parathyroid marker. In addition, the zebrafish pharyngeal arches also express PTH and CasR. And the researchers take it a step further still.
Remember that Gcm-2 is essential for parathyroid formation: mutate it, and the animal doesn’t form a parathyroid. What if we knock out Gcm-2 in a fish? It doesn’t have a parathyroid, after all…all it has are gills.
In zebrafish injected with a morpholino that blocks the Gcm-2 transcription factor, poof, gills fail to form.
So, what we have here are multiple lines of evidence—location, function, several molecular markers, and developmental origins and processes—that converge to show that parathyroid glands and the gills of fishes have a common evolutionary origin.
Okabe M, Graham A (2004) The origin of the parathyroid gland. PNAS 101(51).