Two sets of starting cells
For decades, biology textbooks have described the brain as growing from a single early progenitor cell that gives rise to every part of the organ. A study led by Stanford Medicine, published in Nature Neuroscience on 18 September, says that picture is wrong.
Watching embryos during gastrulation, the stage when a simple cluster of cells organises into body structures, the team identified two distinct groups of neural progenitor cells. The forebrain and midbrain arise from one population. The hindbrain, which controls breathing, heart rate and swallowing, develops from a second population with a separate origin.
"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 Kyle Loh, an associate professor of developmental biology at Stanford and a senior author of the work.
A puzzle in the dish
The discovery grew out of a laboratory problem. Stem cells from the front of the brain were easy to grow in a dish, while cells meant to become hindbrain tissue almost never took. The new work explains why: earlier experiments tried to coax forebrain and midbrain progenitors into becoming hindbrain cells, which the study shows is not possible. Starting from the correct progenitor population, the researchers grew neurons that fired action potentials and produced proteins marking the hindbrain segments that control facial and swallowing muscles.
550 million years of wiring
The team then looked back through evolutionary time. They found the same two-origin pattern in chickens, zebrafish and acorn worms, small creatures on the ocean floor that share a distant ancestor with humans. Jellyfish, which diverged from the human line about 600 to 700 million years ago, keep two nervous systems at different ends of their bodies.
The authors argue that evolution did not invent a brain from scratch. It took two nervous systems that already existed and pushed them together spatially. "Having the brain as one organ would probably be more efficient, but we rely on this primordial way to make the brain as two separate pieces," Loh said. Because the two halves are built by different rules, the finding could change how researchers model conditions such as hindbrain disorders in the lab.