Although philosophers warn us not to mistake the map for the territory, or models of reality for reality itself, the caution is lost on embryonic neurons, which must position themselves with respect to each other during development. Neurons do not start off in the right place, but they can guide each other through their migrations by serving as cellular signposts and emitting molecular signals. If the developing nervous system is imagined as a road system under construction, it is one in which the roads and the signage emerge simultaneously, influencing the locations and directions of subsequent development.
According to a new study, axon bundles can instruct cell body position by acting as border landmarks (axon-restricted migration) or cellular guides. Axon bundles can even appear to influence cell body positioning the way a new multilane road influences settlement patterns—provided one adopts something like a land developer's perspective.
The results of the new study appeared May 11 in Nature Communications, in an article entitled, “Commissural axonal corridors instruct neuronal migration in the mouse spinal cord.” This article described how researchers at Umeå University used genetic changes in mouse embryos to disrupt axonal corridors and make them head in a different direction. When axonal corridors were misdirected, cell bodies from nerve cells also ended up in the wrong place.
“We show here that within the mouse embryonic spinal cord, commissural axons bisect, delimit, or preconfigure ventral interneuron cell body position,” wrote the article’s authors. “Furthermore, genetic disruption of commissural axons results in abnormal ventral interneuron cell body positioning.” Essentially, the axons signal that cell bodies should travel in a certain direction, but not go farther than necessary.
When nerve cells are in the wrong place, neural information is not transmitted properly, and the misplacements can result in dysfunction and neurodevelopmental disorders such as lissencephaly, Kallmann syndrome, and periventricular heterotopia. Misplacements can also happen in common developmental disorders such as dyslexia and autistic spectrum disorders, but it is not clear what role such misplacements play in these cases.
“Because nerve cell position is so important in normal nervous system function and dysfunction we wanted to find out how nerve cells position themselves in the first place. This study uncovered an exciting new mechanism for how this happens,” said senior author Sara Wilson, Ph.D.
“This means the axons from some nerve cells are influencing the position of the cell bodies of other nerve cells meaning that the nerve cells are creating a “map” for other nerve cells to find their way,” she continued. “This is the first time that axons have been shown to act as barriers and it could have important implications for understanding how the nervous system forms in all animals, including humans.”
Overall, this work and other work from the group focuses on understanding the mechanisms (genetic, cellular and molecular) of how the precise “anatomy” of the nervous system first forms and how that influences neuronal function and dysfunction. This basic science research has important medical implications for understanding the cause of some neurodevelopmental disorders: For example do the genes that are associated with such disorders generally control cell body guidance and is that what leads to dysfunction?
“[This work] can also give clues as to how to grow axons during regeneration following damage or disease of the nervous system,” concluded Dr. Wilson. “Can we ‘force’ regenerating neurons to connect properly? In the future, we plan to continue this basic research and find medical research teams to collaborate with to see if our findings are beneficial in these medical contexts.”