Human brain develops from two distinct groups of cells

The origins of the human brain can be traced back to two distinct groups of cells in the developing embryo.

Researchers at Stanford University, California, used mouse genetics alongside human pluripotent stem cells to show that the brain develops from two separate cell populations. The dual origin can be traced back to gastrulation, an important process in early embryonic development. The cell population termed the anterior neural ectoderm gives rise to the forebrain and midbrain, while the posterior neural ectoderm gives rise to the hindbrain.

'We've shown for the first time that the front of the brain arises from a totally different progenitor cell than the back of the brain,' said Dr Kyle Loh, associate professor of developmental biology and senior author of the paper published in Nature Neuroscience.

Advanced mouse genetics methods helped the researchers identify the two progenitor cell populations. The population destined to form the forebrain and midbrain expresses a gene called Otx2, while the posterior population expresses Gbx2. The two cell populations did not overlap during development, with Otx2 marking the anterior population and Gbx2 marking the posterior population.

'In stem cell biology, people are always fixated with creating the end cell type, like the neuron, but it's important to begin at the earliest stages of embryonic development. Our careful attention to that early time point allowed us to find this fundamental split in brain development,' said co-first author Rayyan Jokhai, a graduate student at Stanford University.

After identifying the factors required for hindbrain development, the researchers used human pluripotent stem cells to generate functional hindbrain motor neurons for the first time in the laboratory. The neurons showed electrical activity and molecular characteristics of hindbrain cells, providing a new way to study these cells outside the body.

The researchers said the findings could help future research into conditions affecting hindbrain motor neurons, including spinal muscular atrophy and amyotrophic lateral sclerosis.

'Now we have a model to better understand these devastating diseases, and work toward regenerative therapies for them,' added Jokhai.

The researchers also found evidence of the two-part developmental pattern in other species including macaque monkeys, chickens and zebrafish. They suggest that the two progenitor populations may have been evolutionarily conserved for around 500 million years.

'I was surprised at our findings because the word "brain" implies a contiguous organ that likely has a singular origin,' Jokhai said. 'But even 500 million years ago, there were these separate neural systems, which now almost operate as one, which is very cool.'