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Stanford study finds two distinct progenitor cell types build the vertebrate brain

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Stanford study finds two distinct progenitor cell types build the vertebrate brain

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A Stanford University study published in Nature Neuroscience shows the vertebrate brain develops from at least two independent progenitor cell populations, not one. One lineage forms the hindbrain, while the other gives rise to the midbrain and forebrain. The same dual system appears in species whose common ancestor with humans lived over 500 million years ago.

Key Facts

  • The study, published in Nature Neuroscience, identifies two mutually exclusive progenitor cell populations in 7.5-day-old mouse embryos.
  • One progenitor lineage forms the hindbrain, which controls basic functions like heartbeat and breathing, while the other forms the midbrain and forebrain.
  • Human stem cell experiments showed that early hindbrain progenitors could not be chemically redirected to form forebrain or midbrain cells.
  • The dual progenitor system was found in species ranging from monkeys and chickens to zebrafish and the acorn worm Saccoglossus kowalevskii.
  • The method for growing hindbrain motor neurons could aid research on amyotrophic lateral sclerosis (ALS), where these neurons degenerate.

Two Progenitor Lineages

Researchers at Stanford University labeled cells expressing a hindbrain-specific gene with a red fluorescent marker in mouse embryos 7.5 days after conception. The red label appeared only in the posterior half of the mature brain, while the anterior half showed no fluorescence. RNA sequencing and tissue staining confirmed two mutually exclusive progenitor populations from the earliest stages. Co-author Kyle Loh stated that the cell program is locked at a level that prevents switching between brain regions.

Evolutionary Conservation

The team searched for the dual progenitor system across a wide range of species, including monkeys, chickens, and zebrafish. Both progenitor types were found in every species examined. The separation was also detected in Saccoglossus kowalevskii, a marine invertebrate acorn worm. The common ancestor of humans and this worm lived more than 500 million years ago, before the supercontinent Pangaea formed. Loh said the embryonic development pattern in the worm looks the same as in the mouse.

ALS Research Potential

The study provides an efficient method for growing hindbrain motor neurons, which control functions such as swallowing. Degeneration of these neurons is characteristic of amyotrophic lateral sclerosis (ALS), also known as motor neuron disease. The ability to generate these neurons in the laboratory is important for modeling the disease. This aspect of the research received broad recognition, even from those who disagree with the conclusion of complete independence of the two cell populations.

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