Which Cells Build a Face? A Population That Packs Up and Leaves

Early in development the tissue that will become the brain and spinal cord folds into a tube, and along the ridges where that fold closes a population of cells forms. Rather than staying put, those cells detach from their neighbours, change shape and travel along defined routes through the embryo, sometimes across its entire width. Where they arrive determines what they become, so the same starting population produces wildly different tissues depending on the destination and the signals encountered on the way.

The list is long enough to look like a mistake:

• •Most of the bones and cartilage of the face and skull
• •The nerves and support cells outside the brain and cord
• •Pigment cells in the skin, which is why patterns depend on migration
• •Part of the adrenal gland, producing adrenaline
• •Structures in the heart that divide the outflow vessels
• •Teeth, parts of the eye, and the bones of the middle ear

The population is found only in vertebrates and its appearance is closely tied to what makes them different from their relatives. A head with jaws, paired sense organs, a skull and the capacity for active predation all depend on tissues built by these cells, which is why the group is sometimes described as the fourth germ layer and why its origin is treated as a defining event. Comparing vertebrates with their nearest invertebrate relatives shows related genetic machinery present without the migrating population, which suggests the innovation was assembled from parts that already existed.

Migration is not a wandering search and the cells follow defined corridors laid out in advance by the surrounding tissue. Some regions carry molecules that the migrating cells adhere to, forming a path, and others carry molecules that repel them, forming walls. The result is a set of streams that keep separate from each other even where they pass close by. Cells transplanted from one stream to another frequently adopt the identity of their new position rather than keeping the old one, which shows that the destination is doing more of the deciding than the origin.

Because so many structures depend on one migrating population, disruption produces a distinctive pattern of apparently unrelated defects appearing together. A group of conditions is recognised in which facial abnormalities, heart defects involving the outflow vessels, pigmentation changes and hearing loss occur in combination, and the connection makes sense only in terms of a shared developmental origin. Some are caused by mutations in genes controlling migration or survival, and some by external factors including certain medicines taken in early pregnancy. The pattern is a standard clue that a clinician uses to suspect the underlying cause.

Cells forming along the closing neural tube detach and migrate throughout the embryo, becoming facial bones, peripheral nerves, pigment cells, part of the adrenal gland and structures in the heart, according to where they end up. The population is unique to vertebrates and underlies the jawed predatory head. Disrupting it produces face, heart, pigment and hearing defects together.