Thinking With Our Skin

It’s fascinating to think about how an embryo, a single cell comprising the genetic material of a mother’s egg and father’s sperm, develops into a complex, multi-celled organism with each cell having its own place and function.

I’ve written before about the beginning of the development process,¹ as described by the late Eric Davidson at Caltech, who was working with sea urchin embryos. After the original zygote created by the union of egg and sperm had divided again and again to form a hollow sphere of cells called a blastula, he and his team sacrificed these embryos at subsequent fifteen-minute periods to map out the interaction of genes in the nuclei of these undifferentiated cells. The team discovered that, depending on where in the sphere a cell was situated and time after the blastula formed, one gene would produce a bit of microRNA that moved elsewhere inside the nucleus and promoted another gene to make a different miRNA.

This process of promoting different genes continued—all without coding for any proteins—and directed that particular cell toward becoming a different and unique body part, like a backbone spine or a section of gut. These various bits of microRNA and their interactions formed an instruction set and timing mechanism for developing the entire animal. Davidson’s team then compared these miRNA patterns with other animals that had not shared an ancestor with sea urchins for millions of years and found the mechanism to be “highly conserved”—which means that something similar takes place inside the cells of a human embryo.

In mammals and the vertebrate animals closely related to them by evolution, the blastula sphere develops into the gastrula, a hollow, cup-shaped structure composed of three layers of cells. The inside layer, the endoderm, eventually becomes the gut with associated structures like the small and large intestines and organs like the stomach, pancreas, liver, and lungs. The middle layer, the mesoderm, gives rise to the connective tissues including muscles, bones, bone marrow, and blood and lymphatic vessels, and to associated organs like the heart, kidneys, adrenal glands, and sex organs. The outside layer, the ectoderm, becomes the skin with associated structures like hair and nails, the nasal cavity, sense organs including the lens of the eye and the tongue, parts of the mouth including the teeth, and the anus. The ectoderm also forms the body’s nervous tissue including the spine and brain.

So how does that outer layer of this cup-shaped gastrula become something so interior to our bodies as the brain inside its bony skull and the spine inside its chain of bony vertebrae? The answer is that during embryonic development of this outer layer, the ectoderm acquires what’s called a neural fold. A groove forms in the layer that soon folds over to become a hollow tube, the notochord, which eventually becomes the spine inside its sheath of protective bones. The anterior or front end of the spine becomes the brain. In primitive life forms, the brain remains just a cluster of nerve cells, a ganglia. In more developed organisms—from fish on up to humans—this ganglia develops a complex structure with the brain stem, where consciousness originates; the cerebellum or hindbrain, governing autonomic functions like breathing and balance; the neocortex, governing thinking, speech, and fine motor control; and the limbic system, which is associated with emotions, instincts, moods, and the creation of memories.

It’s no accident that the nervous system arises from the skin, because sensation through the skin is the brain’s first major contact with the outside world. Other structures derived from the ectoderm include the eyes, ears, taste buds, and sense organs in the nasal cavity. It might at first seem that the brain, where the cell bodies of the neurons reside, should form in place and then extend long, thread-like nerve fibers, the axons, down along the spine and out into the skin to get such widespread coverage. But instead they all form in place from the same tissue, starting embedded in the skin.

At the same time that the neural fold is forming the spine and brain, the cup-shaped structure of the ectoderm and endoderm curve around and fuse to form the body cavity. That puts the guts on the inside, the skin on the outside, and the skeleton and muscles somewhere in between. All of these tissues are developing together and sometimes—as with mesoderm muscles of the heart and the endoderm structure of the lungs—merge to form integrated systems.

But how does the developing organism know which end of the spine will become the “anterior” as well as what and where the posterior might be? What directs one end of the hollow tube that represents our bodies to become the mouth and nasal cavity, with their sense clusters, and the other end to become the anus? One further set of genes is needed to manage all this, the homeobox genes, or “hox” for short.

This is another highly conserved gene set. Fish have it, as do frogs, lizards, dinosaurs, birds, and all the mammals. So do the insects and arachnids. The hox genes are only active during embryonic development and determine the major body parts that we share with all these other animals: the head with its brain or nerve cluster, the major sensory organs, and mouth parts; the thorax with the heart, lungs, and nexus of the blood vessels; and the abdomen with its digestive and reproductive systems. In human beings, the thorax is enclosed inside the ribcage and separated from the abdomen by the diaphragm. In insects like the fruit fly and arachnids like spiders, the thorax and abdomen are separate body structures. The hox genes also define the limbs and where they are attached: four limbs connected to the spine in the tetrapods, which developed out of lobe-finned fish and first walked on land—that’s us, along with frogs, lizards, dinosaurs, birds, and all the mammals. Other less closely related animals like insects and arachnids have multiple legs attached to the thorax and sometimes wings, too.

It’s not just a coincidence that we share the same basic body structure with fish and frogs. It’s written into our genes. I always marveled at the movie Avatar, where on the planet Pandora the humanoid natives, the Nav’i, are four-limbed like the Earthly humans, but every other species in close evolutionary proximity to them has six limbs. Given that the hox gene set is relatively stable, creatures so closely related that they can attain near-telepathic communication by mixing the tail ends of their neurons really ought to have a parallel body structure.

The hox gene set is also the reason that we classify mythological creatures like Pegasus, the flying horse; gryphons, which are half lion–half eagle; and dragons, which have four legs and a pair of wings, as “chimera,” or impossible animals. The hox gene set simply doesn’t allow for mashups of six-limbed creatures that closely parallel the known tetrapods. It also forbids angels with two arms, two legs, and a pair of wings. All of them are violations of basic body structure.

We still have a lot to learn about fetal development. And certainly the hox gene set deserves more study. But I find it fascinating that the process of going from a single cell to a complex organism passes through a multi-layered sphere that then folds inward and outward like a piece of origami. And it’s a bit chilling to understand that we all think and feel with cells that originate in our skin.

1. See Learning as a Form of Evolution from December 10, 2017.