Paleontologists used to wonder whether the first teeth were on the inside or the outside of prehistoric bodies. Sharks are covered in thousands of tiny denticles–toothlike nubs of dentine and collagen that make sharkskin coarse to the touch. If the denticles of some very early vertebrate had migrated into the jaw, grown larger and gained new functions, the speculation went, they could have given rise to modern choppers. But over the past decade fossil and genetic evidence has confirmed that teeth are much older than even the ancient shark lineage—indeed, older than the jaw or the denticle. And they originated inside the body, though not in the mouth.

The first sets of teeth belonged to eel-like swimmers that lived some 525 million years ago and ranged from four to 40 centimeters long. Collectively they are known as conodonts for the ring of long, conical teeth in their pharynx. Some fish species still have a set of vestigial teeth in their throat, but pharyngeal teeth for the most part are believed to have migrated forward into the mouth, perhaps as the jaw was evolving.

Supporting that idea, the programmed gene activity that builds teeth differs from the instructions that build a jaw, even though both types of structure grow in tandem. The marriage of tooth and jaw, however, likely gave rise to specialized tooth shapes. By the 10th day of a human embryo’s development, molecular signaling that initiates tooth formation is taking place between two basic embryonic tissue layers. At the same time, signals from the growing jaw imprint a shape onto the primordial tooth that cannot be changed. Even when the bud of a future molar, for instance, is transplanted into a different area of the jaw, the final tooth will become whatever its original location fated it to be.

Unfortunately, dental researchers are finding it difficult to recapitulate half a billion years of evolution in the laboratory. Because burgeoning teeth depend on information from the budding embryonic jaw, work toward generating replacement teeth from dental stem cells focuses on growing them in the desired location in the recipient’s mouth–but scientists are not yet sure the adult jaw can provide the necessary signals to shape made-to-order teeth.