Researchers identify earliest neuron in the embryonic human cerebral cortex

Researchers at Yale School of Medicine and the University of Oxford have identified the very first neurons in what develops into the cerebral cortex, the part of the brain that makes humans human.

The findings published in Nature Neuroscience show that the first neurons, or "predecessors," as the researchers called them, are in place 31 days after fertilization. This is much earlier than previously thought and well before development of arms, legs or eyes.

"These neurons, described here for the first time, precede all other known cell types of the developing cortex," the researchers said in their paper. "These precocious predecessor neurons might be important in the cascade of developmental events leading to the formation of the human cerebral cortex."

The cerebral cortex is largely responsible for human cognition, playing an essential role in perception, memory, thought, language, mental ability, intellect and consciousness. It is composed of about 20 billion neurons and accounts for 40 percent of the brain's weight.

Co-author Pasko Rakic, chair of the Department of Neurobiology and director of the Kavli Institute of Neuroscience at Yale, said the use of highly specific cell markers led the team to the surprising discovery of new types of neurons in the prospective cerebral cortex.

"We hypothesize that these predecessor neurons may be a transient population involved in determining the number of functional radial units including the human specific regions of the cerebral cortex mediating higher cognitive functions," Rakic said. "As a next step it is essential to determine their neural stem cell lineage, pattern of gene expression, developmental role and eventual fate."

Pinpointing the early development of the cerebral cortex may help in understanding the many developmental disorders of higher brain function, such as autism, schizophrenia, childhood epilepsy, developmental dyslexia and mental retardation. It also may explain how the human brain developed differently from that of other species.

Until recently it was thought that cortical neurons were generated locally, but this research team describes a distinctive, widespread population of neurons situated beneath the surface of the human embryonic forebrain even before complete closure of the neural tube.

Predecessor cells, unlike mature nerve cells, do not have synaptic connection with other neurons. They do have long processes, or "tails," with one stretching out in front of the cell body and the other trailing behind. Analysis of the skeleton of these cells suggests that they migrate upwards in the surface of the developing brain and enter the future cortex.

The researchers found that the processes form a vast network and they speculate that this web of processes might be used to control neuronal production, guide the migration of cells and determine the regional specification of the cerebral cortex.

Co-authors include Irina Bystron, Zoltan Molnar and Colin Blakemore of Oxford.