Rouaux and Arlotta examined the animals’ brains under the microscope after four days, at birth, and up to one month of age. In all cases, they found green fluorescent cells not only in layers 2/3, but also in deeper layers. What’s more, the axons from some of the cells extended not to the other side of the brain, but downwards, and expressed genes that are normally active only in layer 5/6 cells. Some had extended into a sub-cortical structure called the thalamus, and others reached the spinal cord. The reprogrammed cells remained stable for at least a month, and further experiments revealed that the capacity for reprogramming persisted until three days of age, but had been eliminated by three weeks of age.

Nevertheless, the findings show that neurons can be reprogrammed long after they differentiated and matured. Researchers have made huge advances in reprogramming cells taken from various parts of the body, but until now it was unknown whether this could also be done in the living body. Although the cells lost the capacity to switch identity when the animals were just three days of age, it may be possible to extend the period of reprogramming to the mature brain.

Layer 5/6 form a pathway called the corticospinal tract, which projects down into the spinal cord and forms connections with motor neurons in the spinal cord, and these in turn connect to muscle cells. The corticospinal tract is essential for voluntary movement, and its cells are damaged in stroke, motor neuron disease and spinal cord injury and various other conditions. The new findings could eventually lead to gene therapies which reprogram cells in the patient’s brain to generate new corticospinal neurons.
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