Language, reasoning, planning, associating and learning; these are just a few examples of higher brain functions attributed to the thin layer of cells on the outside of the brain: the cortex. A study published in Science provides new insights into how those cells get there.
The development of the cortex during embryonic development turns out to be more complex than neuroscientists thought. They assumed that all neurons of the cortex arise from the same stem cells as neurons from deeper brain structures. Their daughter cells grow into neurons and then migrate to the outer layers of the brain. Thus, eventually the cortex arises from different types of neurons that are predominantly organized into six layers. Which type of neuron a cell develops into and which layer of cortex it migrates to would depend solely on the developmental stage of the embryo into which a cell is born.
Gene expression
However, this research shows that cells in the upper layers of the cortex arise from different stem cells than neurons in the lower layers. Researchers at the Scripps Research Institute (USA) discovered this by tracking the gene Cux2 known to be expressed only in neurons of the outer layers of the cortex. As early as 9 or 10 days after fertilization, they saw the Cux2 gene in cells that later developed into to the neurons for the outer layers. The cells that moved to the inner cortex layers appeared to come from a different stem cell type in which the Cux2 gene was not expressed. Even when the researchers forced the Cux2-positive cells to develop before they arrived in the destination layer, they still developed into an outer layer neuron. So it does not matter for these cells where or when they develop into neurons; apparently their fate is determined at birth.
Medical applications
The research not only provides insight into the early development of the brain, but also offers prospects for new avenues of research and medical applications. Now that it is known that neurons from the different cortex layers arise from different types of stem cells, perhaps these different neurons can be grown in the lab. Outer layer neurons are often involved in psychiatric disorders. By creating these, they can be studied more closely. So-called organoids have already helped to better understand conditions such as Fragile X syndrome (characterized by intellectual disability and certain behavioral traits), Angelman syndrome (a developmental delay, abnormal motor and language development and sleep and behavior problems, epilepsy) and Rett syndrome (delays in learning to talk, move and learn).
Author: Daan Schetselaar (2012), edited by Anneke Terneusen (2023)
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