These brain organoids are clusters of lab-grown neurons that mimic structural and functional aspects of full-size brains. Some scientists use these "minibrains" to study brain disorders that can arise during fetal development.
Because it's not possible to directly study these conditions in human fetuses, scientists like Hippenmeyer turn to brain organoids. But the new study, published Aug. 12 in the journal Nature, suggests that organoids may be missing some crucial ingredients that would help them resemble real brains.
A matter of time
In the new study, they used that data as a reference to compare with brain organoids grown from mouse embryonic stem cells. They aimed to see if the developmental sequence in the organoids resembled that in the real brains.
The researchers tracked how neurons developed in embryonic mouse brains and then compared those findings to what they observed in brain organoids. (Image credit: JUAN GAERTNER/SCIENCE PHOTO LIBRARY via Getty Images)During normal brain development, RGPs in the cerebral cortex — the brain's outermost tissues — divide to increase their numbers and then differentiate, forming neurons and glial cells, which help to support, nourish and insulate neurons. In the organoids, however, some RGPs formed neurons too early, while others were still proliferating.
After seeing these patterns, the team investigated the variety of neurons that a single RGP could produce in an organoid. The cortex is made up of six layers of tissue, and normally, an individual RGP can produce both deeper-layer neurons (earlier in development) and upper-layer neurons (in the later stages). But in the organoids, about one-third of the RGPs became restricted to just one of these fates and then couldn't make the other type of neuron.
"This suggests that there is something about the local environment of the cells [in the brain] that gives rise to the neurons," said Denis Jabaudon, a neurobiologist at the University of Geneva who was not involved in the study. However, scientists don't have a precise understanding of what those signals are yet, Jabaudon said.
Related storiesFor neurons to find each other, they have to be in the right place at the right time, Jabaudon added. "So, if you shift the timing of development, you're going to be shifting the opportunities for connections and the opportunities for specific circuits" to form, he told Live Science.
Once these missing ingredients are identified, this could "open the door" to systematically add back those signals in organoids in a way that would mimic the real brain closely, he told Live Science. Hippenmeyer added that the team also plans to grow brain organoids with human cells and investigate the same questions.
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