Nerve cells need a lot of energy and oxygen. They receive both through the blood. This is why nerve tissue is usually crisscrossed by a large number of blood vessels. But what prevents neurons and vascular cells from getting in each other's way as they grow? Researchers have identified a mechanism that takes care of this. The results have now appeared in the journal Neuron. 

Nerve cells are extremely hungry. About one in five calories that we consume through food goes to our brain. This is because generating voltage pulses (the action potentials) and transmitting them between neurons is very energy-intensive. For this reason, nerve tissue is usually crisscrossed by numerous blood vessels. They ensure a supply of nutrients and oxygen.

During embryonic development, a large number of vessels sprout in the brain and spinal cord, but also in the retina of the eye. Additionally, masses of neurons are formed there, which network with each other and with structures such as muscles and organs. Both processes have to be considerate of each other so as not to get in each other's way. "We have identified a new mechanism that ensures this," explains the senior author.

"The appearance of blood vessels in the spinal cord begins in the animals about 8.5 days after fertilization," the author says. "Between days 10.5 and 12.5, however, blood vessels do not grow in all directions. This is despite the fact that large amounts of growth-promoting molecules are present in their environment during this time. Instead, during this time, numerous nerve cells - the motor neurons - migrate from their place of origin in the spinal cord to their final position. There, they then form extensions called axons that lead from the spine to the various targeting muscles."

This means that the motor neurons self-organize and grow at the time that blood vessels do not grow towards them. Only then after, do the vessels begin to sprout again. "The whole thing resembles a carefully choreographed dance," explains the doctoral student. "In the course of this, each partner takes care not to get in the other's way."

But how is this dance coordinated? Apparently, by the motor neurons shouting a "stop, now it's my turn" message to the vascular cells. To do this, they use a protein that they release into their environment - semaphorin 3C (Sema3C). It diffuses to the vascular cells and docks there at a receptor called PlexinD1 - in a sense, this is the ear for which the molecular message is intended.

"When we stop the production of Sema3C in neurons in mice, blood vessels form prematurely in the region where these neurons are located," explains the senior author. "This prevents the axons of the neurons from developing properly - they are prevented from doing so by the vessels." The researchers achieved a similar effect when they experimentally stopped the formation of PlexinD1 in the vascular cells: Since these were now deaf to the Sema3C signal from the neurons, they did not stop growing but continued to sprout.

The results document the importance of coordinated operation of the two processes during embryonic development. These findings could also contribute to a better understanding of certain diseases, such as retinal defects caused by strong and uncontrolled vessel growth. The use of the newly discovered mechanism may also potentially help in regenerating destroyed brain areas, for example after a spinal cord injury, in the long term.

https://www.cell.com/neuron/fulltext/S0896-6273(22)01078-9

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fendothelial-plexind1&filter=22