Introduction
Have you heard the story of Homer’s Achilles? The greatest of all the Greek warriors,
Achilles was blessed at birth to be physically invincible to any weapon with the exception of his left heel. Despite these protective measures, he was killed by the Trojan Prince Paris, who targeted Achilles’ heel and had shot an arrow between his armor’s bindings. While the myth of Achilles can serve as a cautionary tale that even the most prepared person can meet unexpected ends, it also provides a warning to the “Achilles” harbored within the human body: the central nervous system (CNS).
Composed of both the brain and spinal cord, the CNS’s main purpose is to synthesize sensory information collected from throughout the body and to respond by coordinating conscious and unconscious reactions. For instance, on a bright day, your brain might receive a message through the spinal cord that the sun is hurting your eyes. In response, your brain would then have the spinal cord relay a message to your hands about shielding your eyes from the sun. These types of complex movements are primarily facilitated by the brain, although the spinal cord is responsible for more basic muscle reflexes, like squinting at bright stimuli. The CNS is a sophisticated system,; critical in processing and generating responses to external stimuli, so naturally any mutations, damage, or deterioration of the CNS could significantly alter a person’s quality of life.
Genetic Anomalies and their Domino Effect on Fetal Formation
In embryonic development, the CNS begins as a sheet of cells, until around week five, when it folds into a tube. From there, the codle, or lower end of the tube, extends to form the spinal cord while on the opposite side, (the cranial end,) enlarges to form the brain. Although it sounds simple, other developments within the embryo can make it challenging for the sheet of cells to fold properly. In some cases, the tube does not fully close when it is supposed to and is then forced to remain open throughout the remainder of development. Conditions , such as these, where the spinal cord, (which at this point in development is referred to as neural tube), fails to close properly are known as a neural tube defects (NTD). NTDs are the most common CNS structural defect, currently affecting around 5% of all children. The closer to the cranial end the NTD occurs, the more limited the functions of the CNS are.
The main mission of Joseph Gleeson, the Principal Investigator of the PI of Gleeson Lab’s, main mission is to explore and understand the genetic implications of a specific type of NTD: spina bifida. Spina bifida is a condition in which the spinal cord does not close properly, inhibiting the formation of the backbone. In addition to leaving the spinal cord more exposed to extraneous dangers (i.e. accidents), it also limits the brain’s range of communication with the body. Through genome sequencing, the process of extracting and sequencing DNA for abnormalities, Dr. Gleeson and his team study saliva samples from families with spina bifida, to determine which genes are linked to the conditionspina bifida. By sequencing the genetic materials of the parents and child (trio-exome sequencing), the Gleeson Lab is able to identify genes responsible for causing spina bifida. The Lab’s ultimate goal is to improve understanding of the genes responsible for spina bifida and develop treatments, particularly in those that seem most severe.
Axon Regeneration: Can the CNS recover to full function after traumatic axonal injury?
On the opposite end of the age spectrum, Ph.D students Camilo Londoño and Kween Agba at the Zheng Lab are observing the regenerative abilities of axons. Axons are clusters of cells that relay information through electrical signals from sensory receptors to the CNS and to all organ systems within the body. Like most mitotic cells within the body, axonal regeneration significantly declines due to aging and the resulting dysfunction of cellular regulation. The Zheng lab specifically studies the regenerative abilities of white matter, or nerves covered in insulating myelin sheaths that conduct electrical impulses at a faster rate than their unmyelinated, grey matter counterparts. While there are protein inhibitors within certain types of neurons that limit their capacity to regenerate, those in the Zheng lab note that neurons associated with the CNS are especially resilient to regeneration due to their limited interaction with genes that upregulate their growth.
Given that the spinal cord is essential for sensory and motor communication between the brain and the peripheral nervous system, studying axonal regeneration through the epistasis, – or interactions between genes, – could allow researchers to form therapeutic strategies that bolster expression of regenerative mechanisms. Understanding these mechanisms is especially important for those individuals who experience physical trauma to their CNS due to astroglial scar formation. Astroglial scars are , formed when types of neurons called astrocytes form around a wound in nervous tissue.,They then release proteins onto the surface of the surrounding nervous tissue called chemokines. Though these chemokines are beneficial to tissue healing by stimulating surrounding infection-protecting leukocytes, another set of proteins called proteoglycans were found to be the primary inhibitory molecules for axon regeneration. It is the hope of the Zheng lab that the genes and receptors associated with proteoglycan uptake are uncovered and can be interfered with to revitalize damaged axons and increase their regenerative capacity.
So, what can we do with this information?
As CNS trauma and genetic neural diseases are both difficult to predict and, – at times, – unavoidable, furthering our understanding of which proteins and genetic pathways influence their prevalence and severity betters the quality of life for those affected and our collective understanding on how to prevent these mechanisms in the future. Importantly, as seen from the Gleeson lab, environmental factors like ease of nutrient procurement like folate and vitamin B12 can aid greatly in preventing neuronal damage from being passed onto future generations. Just as Achilles sought to protect himself and his loved ones from those who came to harm them, we should consider the impact of our actions on our central nervous system in every choice that we make.