Mysterious Brain Cells That Disappear During Development Don't Actually Disappear

The subplate neurons of this developing cortex are highlighted in green. These cells were thought to disappear entirely, until now. Laboratory of Stem Cell Biology and Molecular Embryology/The Rockefeller University

As babies develop in the womb, brain cells called subplate neurons appear in their brains. Mysteriously, these neurons disappear during postnatal development. Well, at least scientists thought they did. Now researchers have spotted these sneaky cells in adult brains for the very first time.

At certain points during development, the subplate zone is one of the biggest areas of a fetus’ brain, but it was widely accepted that subplate neurons disappear at some point after birth. However, recently scientists have found that these vanishing cells are genetically similar to certain neurons linked to autism, causing researchers to wonder whether subplate neurons actually disappear after all.

So, scientists led by the Rockefeller University took it upon themselves to find out. Publishing their findings in the journal Cell Stem Cell, the team discovered that subplate neurons don’t just suddenly disappear, instead they become part of the cerebral cortex – an important part of the brain involved in memory, thought, language, and consciousness, among other things.

“The understanding about the subplate was that it expands and then the cells of the subplate just die out,” said study author Ali H. Brivanlou in a statement. “But we hypothesized: What if these subplate cells are not dying? What if they’re just moving to a different level of the cortex – becoming part of the cortex?”   

The team examined brain tissue from various points in development and noticed a protein called PRDM8. Spotting this protein was important because it is normally expressed in neurons that migrate to a new location and helps cells move to the brain’s cortical plate. They then found that subplate-like neurons formed from stem cells also contained PRDM8, while lab-grown subplate neurons appeared to migrate from their original position. Therefore, the researchers realized the subplate neurons must simply be moving, not dying off.

Subplate neurons sneaking away from their original positions. The Rockefeller University

Not only did the researchers find that the cells survived and moved, they also discovered that they mature into a number of different types of deep projection neurons, cells found deep within the cerebral cortex.

The team also found that they could manipulate what kind of projection neurons were produced. By altering WNT signaling – a process that regulates things like cell migration – they could produce either projection neurons suited to the cortex or projection neurons found elsewhere.

Better understanding projection neurons and finding ways to manipulate them is important because problems with these cells are linked to certain disorders like autism.

“A lot of the genes associated with autism are first expressed in the subplate,” explained first author Zeeshan Ozair. “And if subplate neurons don’t die but instead become part of the cortex, they will carry those mutations with them.”

The researchers hope that their results might contribute to finding ways to treat diseases that kill off deep projection neurons in the brain, like Alzheimer’s, Huntington’s disease, and amyotrophic lateral sclerosis (ALS).

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