Our brain may be a hybrid of two ancient nervous systems that were packaged together hundreds of millions of years ago. This is based on the finding that the front and back brain regions in people and several other species develop from two distinct cell types in embryos, instead of sharing the same developmental origin, as previously thought. One type expresses a gene called OTX2 and turns into the neurons found in the front part of the brain, comprising the forebrain and midbrain.
The other expresses a gene called GBX2 and becomes the neurons in the back part of the brain, the hindbrain. The researchers then conducted experiments using human cells in a dish and found that the neurons of the hindbrain and those of the forebrain and midbrain also develop from different progenitor cells. This explains why it has been so hard to grow human hindbrain tissue in a lab.
Researchers have typically tried making hindbrain neurons from the progenitor cells that are destined to become forebrain and midbrain neurons, which doesn’t work, he says. Armed with this knowledge, the team was able to grow functional human hindbrain motor neurons in a dish for the first time by starting with the correct type of progenitor cell. The hindbrain coordinates fundamental life-sustaining processes, such as breathing, sleeping, eating and the beating of the heart, whereas the forebrain is the centre of higher-level thought.
Conditions like amyotrophic lateral sclerosis (ALS), the most common type of motor neuron disease, and spinal muscular atrophy cause speech and swallowing difficulties because they affect the hindbrain. Recently, scientists also discovered that GLP-1 drugs like Ozempic and Wegovy suppress appetite in mice by acting on the hindbrain. Now that it is easier to grow human hindbrain neurons in a dish, it should assist ALS and spinal muscular atrophy research, and allow us to investigate the precise mechanisms of how GLP-1 drugs work in people, says Loh.
When does your brain reach adulthood? We’re now understanding the many ways the organ continues to mature decades after society first deems you an adult The researchers also studied early-stage embryos of chickens, zebrafish and acorn worms, and found their nervous systems are similarly derived from two different types of progenitor cells. This suggests our shared two-origin brain system arose at least 550 million years ago.
But jellyfish, which we diverged from around 600 to 700 million years ago, have two separate nervous systems. These may have joined up in our distant ancestors because it improved their overall processing power, says Loh. Having our brains develop along two separate pathways might also have facilitated the evolution of complex thought, says Loh.
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