Magic embryology: What guides nerve pathways to muscles? (Introduction)

by David Turell , Saturday, March 23, 2019, 17:48 (1859 days ago) @ David Turell

Controls are described:

https://medicalxpress.com/news/2019-03-mountaineers-nerves-expert-guidance.html

"...the nervous system relies on elaborate timing and location of guidance cues for neuronal axons—threadlike projections—to successfully reach their destinations in the body. Now, Salk Institute researchers discover how neurons navigate a tricky cellular environment by listening for directions, while simultaneously filtering out inappropriate instructions to avoid getting lost.

"'There are 100 trillion connections in the nervous system governed by 20,000 genes, of which roughly 10 gene families are known to be involved in controlling axon guidance. We wanted to understand the clever genetic systems nature has employed to wire the most complicated biological machine in the universe," says Salk Professor Samuel Pfaff, senior author and a Howard Hughes Medical Institute investigator. "Thus, we set out to examine how motor neurons find their connections with muscles in the body, which is critical for our brain to relay information to our muscles to allow for movement."

"The brain controls hundreds of different muscles to allow for precise movement. During development, motor neurons in the spinal cord extend their axons outside of the central nervous system to connect with muscle cells in the body. Every motor neuron relies on a set of genes to ensure the axon grows correctly to the muscle.

***

"Upon closer investigation, the scientists found that these motor neurons climbed up the edge of the spinal cord rather than properly exiting to meet their muscle targets. The team pinpointed the gene causing this detrimental mutation as p190, which was previously known to play a role in cancer suppression, but had not been implicated in establishing neuronal connections during development.

"The researchers set up a series of experiments to examine how p190 affects axons leaving the spinal cord. They found that, although axons are normally attracted to a protein in the spinal cord called netrin, during a short time window p190 acts as a blinder, so the axons disregard netrin and are led outside of the spinal cord. After the axons safely leave the central nervous system, this blinder is removed. Without p190, the axons are attracted to netrin and do not properly leave the spinal cord, so never connect with muscles.

"Pfaff, holder of the Benjamin H. Lewis Chair, adds, "These results provide mechanistic insight into the unimagined complexity that cells use to communicate with one another.'"

Comment: Another feedback loop to control development which still has to show how an exact path to the correct muscles is fully controlled over the distance: in a six-foot human flexing his big toe the route is roughly six feet!