Neuron: How nerve and vascular cells grow in harmony

Nerve cells need a lot of energy and oxygen
.
They receive both substances
through their blood.
This is why neural tissue is usually crossed
by a large number of blood vessels.
But what prevents neurons and vascular cells from blocking each other during growth? Researchers at the Universities of Heidelberg and Bonn, together with international partners, have identified a mechanism
to address this problem.
The findings have been published in the journal Neuron.

Nerve cells are extremely hungry
.
About one-fifth of the calories we consume through food go to the brain
.
This is because generating voltage pulses
(action potentials) and passing them between neurons is very energy-intensive.
As a result, neural tissue is often crossed
by many blood vessels.
They guarantee a supply
of nutrients and oxygen.

During embryonic development, a large number of blood vessels germinate in the brain and spinal cord, as well as in the retina of the eye
.
In addition, a large number of neurons are formed there, and they are connected to each other and to structures such as muscles and organs
.
These two processes must be considerate of each other so as not to get in the way of the other
.
"We have identified a new mechanism to ensure this," explains Professor Carmen Ruiz de Almodóvar, a member of
the University of Bonn's Immunosensory Cluster of Excellence and the interdisciplinary research area of Life and Health.

The researchers were transferred to the Institute of
Neurovascular Cell Biology at the University Hospital Bonn in early 2022.
Since this spring, she has held a specially established Schlegel professorship, which aims to attract outstanding researchers to Bonn
.
However, much of the research is still done at her old place of work, the European Center for Vascular Science at the Mannheim Medical School, which is part of the University of
Heidelberg.
The work was subsequently completed
at the University of Bonn.
In her research, she and international partners took a closer look at the formation
of blood vessels in the spinal cord of mice.

The spine stops growing

"Animals start showing blood vessels
in the spinal cord about 8.
5 days after fertilization," she said.
"However, between days 10.
5 and 12.
5, the blood vessels do not grow
in all directions.
Although during this time, there are a large number of growth-promoting molecules
in their environment.
Instead, during this time, a large number of nerve cells — motor neurons — migrate from their place of origin in the spinal cord to their final location
.
There, they form an extension called axons, which extend from the spine to various target muscles
.
”

This means that motor neurons organize and grow on their own when blood vessels do not grow
towards them.
Only after that the blood vessels begin to sprout
again.
"The whole thing was like a choreographed dance," explains
José Ricardo Vieira.
PhD students in Ruiz de Almodóvar's research group did most of the work
in this study.
"In the process, both sides are careful not to get in the way of the other
.
"

But how is this dance coordinated? Apparently, the message
"Stop, now it's my turn" is sent to the vascular cells through motor neurons.
To do this, they use a protein that is released into the environment, signalin 3C (Sema3C).

It spreads to blood vessel cells, where it docks on a receptor called PlexinD1 — in the sense that that's where the molecular message is delivered to the ear
.

The blood vessel cells of deafness grow uncontrollably

"When we stopped the production of Sema3C in mouse neurons, the regions where these neurons were located prematurely formed blood vessels," explains
Professor Ruiz de Almodóvar.
"This hinders the normal development of neuronal axons – blood vessels prevent them from doing so
.
" When the researchers experimentally stopped the formation of PlexinD1 in vascular cells, they achieved a similar effect: Since these cells now deaf to the Sema3C signal emitted by neurons, they did not stop growing, but continued to germinate
.

The results demonstrate the importance of
these two processes working in harmony during embryonic development.
The findings also contribute to a better understanding of certain diseases, such as retinal defects
caused by the growth of powerful and uncontrolled blood vessels.
In the long run, using the newly discovered mechanism may also help regenerate damaged brain regions, such as after
a spinal cord injury.