A new study published in Nature Neuroscience shows evidence that our brains are actually two organs combined into one composite organ. You may be thinking that I am referring to the two hemispheres of the brain, but I am not. The notion that our two brain hemispheres function independently is largely a myth—they are massively interconnected with many neural circuits spanning both hemispheres.
Rather, the study was looking at the earliest embryonic origins of the forebrain, midbrain, and hindbrain. The forebrain is the cerebral cortex, the most recently evolved thinking part of the brain. It also contains the thalamus, hypothalamus, and basal ganglia. The midbrain is a small region at the top of the brainstem that includes the substantia nigra, periaqueductal gray, red nucleus, and other structures. They are the interconnection between the brain and the cerebellum and the cortex and brainstem. The hindbrain is essentially the brainstem, which contains primitive circuits for breathing, autonomic function, and connections to the spinal cord. The anterior hindbrain also contains the cerebellum, which acts as a separate brain for coordination.
Up until now, it was thought that the brain develops from one common neuroectoderm stem cell—one stem cell that becomes the entire nervous system. This makes intuitive sense since the nervous system functions as an integrated whole and is comprised of the same kind of cells and tissue.
What this new study finds, however, is that the forebrain and midbrain derive from an anterior neural ectoderm stem cell, while the hindbrain derives from a posterior neural ectoderm stem cell. These two lineages never overlap, meaning that they emerge at the same time during gastrulation, but they do not share common neural stem cells. Therefore, it seems that evolutionarily they represent two independent parallel nervous systems that were later fused into one composite organ.
This study was done on the mouse brain, but they then demonstrated the same two-origin system in chickens, zebrafish, and acorn worms, showing that this split goes back 550 million years to hemichordates.
While all this is fascinating, why is this medically relevant? Well, researchers commonly use stem cells and then coax them to develop into specific cell types, so that they can study them and use them to model different diseases. Up until now, it has been difficult for researchers to derive hindbrain cells from these neural stem cells, which has frustrated research. Now the reason appears to be clear: those stem cells can only become forebrain and midbrain cells—they cannot become hindbrain cells. These two developmental paths are already committed, with different gene expression, and cannot cross over.
This new study opens up the possibility of creating hindbrain cell lines for study. In fact, the researcher did coax posterior neural stem cells to become hindbrain motor neurons, with all the characteristics of those cells. For basic science research like this, it is easy to speculate or claim that it might lead to medical breakthroughs in the future, and of course this is no exception. This is no guarantee, but historically such basic science findings do lead to downstream benefits.
In this case, there is a strong case to be made that the ability to develop authentic hindbrain cell lines will be a boon to research, including research looking into the causes and potential treatments for specific diseases, like motor neuron diseases that affect hindbrain motor neurons. It will take years, perhaps decades, to realize these downstream benefits, but they will likely come. This research (if it holds up, which seems likely) does relieve a significant frustration for those studying the hindbrain and diseases that affect it.
