Growth health of motor neurons guided by ‘love-hate relationship’ with blood vessels

A new collaborative study shows how blood vessel gene It plays an important role in motor neuron development by directing blood vessels out of the way. This finding has important implications for understanding diseases in which motor neuron connections are disrupted, such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).

Now, a new collaboration between scientists at the Salk Institute and colleagues at the San Raffaele Institute of Science in Italy suggests that vascular genes play an important role in motor neuron development by telling blood vessels to stay out of the way. It shows that you are fulfilling

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The findings, published in the journal Neuron on October 7, 2022, found that “push-pull” relationship with blood vessels By pulling blood vessels into and out of the way of growing neurons, they guide the growth and development of motor neurons, and potentially many different cell types throughout the body. This finding also has implications for understanding diseases in which motor neuron connections are disrupted, such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).

“This discovery reveals a set of previously ununderstood molecular and cellular interactions,” said Professor of Gene Expression Lab and holder of the Benjamin H. Lewis Chair at Salk University. Co-corresponding author Samuel Puff said. “Discovery of how these genes regulate blood vessel growth and neuronal development will help us understand how other brain circuits form, and how cancer cells interact with the environment. It has many meanings, even to understand what

Motor neuron connections are formed during fetal development. This process of wiring the nervous system is so precise that cells make trillions of connections that reach throughout the body. However, the genetic processes that guide this development are still poorly understood.

Previous research has focused on the role of specific genes directly related to motor neurons and how they develop. But in this study, scientists took a more holistic approach, looking at genes both inside and outside the nervous system.

Researchers randomized genetic mutations in mice and closely examined the animals’ developing motor neurons. Surprisingly, they discovered that mice whose motor neurons were not growing properly had mutations that affected the vascular system, including blood vessels, rather than the nervous system.

In healthy mice, motor neurons grow from the spinal cord and can navigate through surrounding tissues to reach distant muscle groups. appeared to get stuck behind the vascular barrier. I found

“There is a clash between growing axons and vascular cells,” says group leader in molecular neurobiology at the San Raffaele Science Institute in Milan, Italy, and co-chair, formerly at Salk. Author Dario Bonanomi says: “If you remove this receptor from vascular cells, motor axons collide with blood vessels, compromising and blocking their progression to muscle.”

This finding sheds light on the delicate dance of developing neurons. Neurons need to attract blood vessels to promote growth while simultaneously repelling them out of the way. This is relevant to addressing the hurdles that must be overcome in the development of stem cell-based motoneuron ‘replacement therapies’, which are potential treatments for motor neuron degenerative diseases such as ALS and SMA. I’m here.

In the future, we plan to examine the ‘crosstalk’ between nerves and blood vessels in other contexts and how the nervous and vascular systems respond to stroke, brain injury, and degenerative diseases such as ALS and SMA. is.

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