New study suggests the human brain has two independent cellular origins

Traditional biology has long supported the idea of the brain stemming from a single cell type in the brain. Nevertheless, what if a recent study, led by Stanford Medicine, suggests that the brain may be built from two separate cellular lineages that develop in parallel. What are the implications for our understanding of evolutionary neuroscience?

Stanford Medicine recaps that scientists initially believed that the entire brain (front, middle and back) could be traced back to one common neural progenitor cell type from stem cells when an embryo’s basic cell layers are laid down. However, this recent study, combining experiments on mouse embryos and human stem cells, shows that the brain arises from two independent cell lineages that develop simultaneously. These two cell lineages are called the anterior neural ectoderm (aNE) forming the front and core of the brain, and the posterior neural ectoderm (pNE), forming the hindbrain.

All cells contain all the genes you have. During the development of an embryo, some genes are silenced in certain cell types, allowing your cells to have different shapes and functions, but the same genetic code. The brain cell types are associated with the expression of two different genes exclusive to each lineage. Furthermore, by genetically labelling the pNE descendants, the researchers found that they stayed almost entirely in the hindbrain.

In human stem cells grown in a dish, each cell type largely resisted signals pushing it towards the other’s fate. Whether this fate determinism would be observed in a real embryo has not yet been tested.

Chicken, zebrafish and acorn worms, which shared a common ancestor with us over half a billion years ago, also showed the same two gene-activity patterns.

As the two cell lineages eventually build one connected organ, the brain has long appeared to be a single unit. Moreover, the researchers estimate this two-origin pattern as being 550 to 600 million years old.

Kyle Loh, one of the authors of the paper, points to jellyfish possessing two separate nerve nets on opposite ends of its body. He suggests that in one of our distant ancestors, a nervous system like this was gradually pushed together through evolutionary time, to increase efficiency of communication.

Scientists have long tried with difficulty to culture hindbrain cells in the lab with the goal of better understanding diseases that compromise key components of the brain such as the brainstem, impairing the ability to speak, move, or eat. New Scientist reports that according to Loh, while researchers were trying to tweak the chemical signals to turn neural stem cells into the desired type, they were unsuccessful. What was actually encumbering their progress was the use of forebrain progenitor cells, which are genetically distinct and would not comply. Once this was understood, they were able to grow functional human hindbrain motor neurons that could fire electrical signals, pointing to the possibility of real developments in the understanding of hindbrain-related disease.

Loh says the advance could help research into diseases like ALS (amyotrophic lateral sclerosis), a neurodegenerative disorder that results in the gradual and fatal loss of motor neurons.

This discovery does not completely eliminate the possibility of a pan-brain progenitor in the embryo before the two groups diverge; however, what they can propose based on their results is that the brain is a composite organ, formed from two parallel starting populations. It does also suggest an interesting angle of how the human brain potentially came to be, and what its antecedents in ancestors may have looked like.