A molecular code that distinguishes a group of muscle-controlling nerve cells collectively is known as the phrenic motor column (PMC). These cells lie about halfway up the back of the neck, just above the fourth cervical vertebra, and are probably the most important motor neurons in your body.
Harming the part of the spinal cord where the PMC resides can instantly shut down breathing. Little is known about what distinguishes PMC neurons from neighboring neurons, and how PMC neurons develop and wire themselves to the diaphragm in the fetus. PMC cells relay a constant flow of electrochemical signals down their bundled axons and onto the diaphragm muscles, allowing the lungs to expand and relax in the natural rhythm of breathing
To find out what distinguishes PMC neurons from their spinal neighbors in mice, a retrograde fluorescent tracer was injected into the phrenic nerve, which wires the PMC to the diaphragm, and then the spinal neurons that lit up as the tracer worked its way back to the PMC. The Researchers used transgenic mice that express green fluorescent protein (GFP) in motor neurons and their axons, in order to see the phrenic nerve. After noting the characteristic gene expression pattern of these PMC neurons, he began to determine their specific roles. Ultimately, a complicated strain of transgenic mice, based partly on mice, revealed two genes, Hoxa5 and Hoxc5, as the prime controllers of proper PMC development. Hox genes (39 are expressed in humans) are well known as master gene regulators of animal development.
When Hoxa5 and Hoxc5 are silenced in embryonic motor neurons in mice, the scientists reported, the PMC fails to form its usual, tightly columnar organisation and doesn’t connect correctly to the diaphragm, leaving a newborn animal unable to breathe. Even if you delete these genes late in fetal development, the PMC neuron population drops and the phrenic nerve doesn’t form enough branches on diaphragm muscles.
These findings help to understand the wider circuitry of breathing – including rhythm-generating neurons in the brain stem. These are in turn responsive to carbon dioxide levels, stress, and other environmental factors. Now that you have awareness of PMC cells, you can work your way through the broader circuit, to try to figure out how all those connections are established.
After you fully understand how the respiratory network is wired, you can begin to develop novel treatment options for breathing disorders such as sleep apnoeas.
