Table of Contents

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Table of Contents

Molecular Design of the Spine and Spinal Cord

Table of Contents

Abstract

This paper discusses the molecular aspects of the spine and the spinal cord. It explores the purpose of the spinal cord and how it operates in the body. The report then investigates how evolution has changed the spine and spinal cord of numerous species such as different reptiles, fish, and birds. Furthermore, the mechanisms involved in the synthesis of cells involved in the spinal cord are discussed.

Introduction

While our brain is surrounded and protected by the skull, our spinal cord is covered and preserved by the spine. The main purpose of this essay is to discuss the differences in the development of the chorda and the spine from a molecular, structural, and functional perspective.

To begin with, acknowledging that 90 % of animals do not have a spine and are fine without back bones (the invertebrates) (Gabbatiss, 2016), it is crucial to emphasize the importance of the spine for the proper functioning of the human body. Undoubtedly, the body would not be able to operate without it just like the brain would not be able to send messages to the rest of the body. Therefore, it has a vital role. Thanks to the spine, humans have the ability to stand up and keep upright. The spine is not only designed to provide structure and support to the body, sit also allows the freedom of movement and the ability to bend easily with flexibility. Additionally, the spine is designed to protect our spinal cord (“A Patient’s Guide to Anatomy and Function of the Spine” | University of Maryland Medical Center, n.d.). The fundamental features of the spine such as its ability to provide stability, flexibility, strength but also protection, make it a potential basis for bio-inspired technologies.

An Introduction to the Operation of the Spinal Cord

The spinal cord is contained into the spinal column and measures about 45 centimeters in an adult (“Anatomy of the Spine and Peripheral Nervous System” | American Association of Neurological Surgeons, n.d.). Without it, any human would not be able to move any part of its body and the organs would not function. The spinal cord begins underneath the brainstem (which corresponds to the posterior part of the brain) and is divided into several segments. As shown in Fig. 1 and 2, the cervical, thoracic, lumbar, sacral, and coccygeal segments of the spinal cord are defined according to the division of the vertebral column. Each of them has spinal nerves associated to them, in all there are 31 pairs of nerves. Indeed, 8 pairs of nerves are contained in the cervical part of the spine, 12 in the thoracic, 5 in the lumbar, 5 In the sacral and 1 in the coccygeal (Frost et al., 2019).

Fig. 1 The structure of the segments of the spine. [Adapted from Highsmith, “Spinal Anatomy Center”]
Fig. 2 The link between the spine and the brain. [Adapted from “Why is the spinal cord important” | Coloplast Care, n.d.]

In each vertebra, there are two nerve roots (the dorsal and the ventral) that come out of the spinal cord and connect to a single spinal nerve on each (Nall, 2019). As shown in Fig. 3 and 4, the spinal cord is also composed of grey matter and white matter surrounding it. The white matter contains axons (corresponding to thin fibers that conduct electrical impulses away from a neuron) and stimulate faster nerve transmission while the grey matter is composed with synapses which establish a junction between two nerve cells (Nall, 2019).

It is necessary to highlight the key role the spinal cord plays in the good functioning of the body. Indeed, the main functions of the spinal cord are to carry information to the brain, carry signals from the brain and to conduct motor reflexes. These different types of information are carried by the two nerve roots of each vertebra (Nall, 2019).

Fig. 3 How the spinal cord is organized. [Adapted from Rye et al., “Figure 35.25”]        
Fig. 4 A schematic cross section of the spinal cord and the dorsal and ventral roots. [Adapted from Maiese, 2020]

Each nerve root conveys very specific information. The dorsal nerve root, or posterior root, carries sensory messages such as information about touch, pressure, temperate or even pain from our body to the brain (“Why is the spinal cord important” | Coloplast Care, n.d.). A ganglion (called the dorsal root ganglion) lies on each dorsal nerve. Generally speaking, a ganglion is any area that houses cell bodies of neurons outside of the central nervous system. In this case, the ganglion houses the cell bodies of the sensory (mostly bipolar neurons). To get to the brain, the information carried by the dorsal nerve root needs to get into the grey matter of the spinal cord first (Nall, 2019). Meanwhile the ventral nerve root, or anterior root, is the efferent motor root as it carries signals from the brain destined to control motor function. It is responsible for transmitting output from the brain and spinal cord to the body’s muscle. Instead of being housed in a ganglion, the cell bodies of the efferent motor fibers are housed in the anterior horn of the spinal cord (Kaiser and Lugo-Pico, 2020).

To illustrate the particular function of these two nerve roots, let us see how the receptor reflex arc, which describes the link between the system of sensation, decision and reaction, is processed through the spinal cord itself and not the brain (Fig. 5). The system in place in our body that allows us react quickly to exterior stimulus is called reflex reaction as it provides immediate and unconscious reaction to avoid danger. When our safety demands quick responses, the signals bypass the brain and act upon as soon as they reach the spinal cord. Indeed, the signals reaches up the spinal cord carried by the dorsal neuron and heads straight back out to the motor neuron to produce a quick response. This system emphasizes one of the key roles of the spinal cord (Chung, 2019).

Fig. 5 The Receptor Arc. [Adapted from Chung, 2019]

Commonalities and Disparities Between the Spines of Different Organisms

Most vertebrates are quadrupedal animals, meaning they are using four limbs or legs to move. However, there are some species, including humans, who walk on their two feet called the bipeds. For instance, birds are biped when they are not flying, as well as several lizard species when they are running from predators or even kangaroos. For these species who adopted the bipedal locomotion, the alternated loading conditions and movements requirements subsequently led to different changes and adaptation in the structure and the design of the spine in different species (Galbusera and Bassani, 2019).

The ornothodirans, which are birds’ ancestors, adapted to these changes by developing a more flexible neck as well as a more rigid lower back. These adaptations, including the horizontal trunk alignment, remain in existing birds. Moreover, birds have hallowed bones, and therefore very light bones which allows the body’s static equilibrium (Galbusera and Bassani, 2019).  

For humans, primitive bipedalism involves other mechanisms. When humans stand erect, the spine is predominantly vertical, therefore a heavy tail balancing the weight of the body is not essential (Galbusera and Bassani, 2019). Indeed, humans mostly stand upright unlike non-bipedal mammals. This new posture necessitated major changes in the anatomy of the vertebral column.

Furthermore, when humans are standing upright, the trunk’s weight induces a compression loading on the vertebral column. Indeed, the spinal loading in human standing is represented by a compressive load following the shape of the spine. On the other hand, the spine of quadrupeds experiences an extension loading in a horizontal posture (Fig. 6). In quadrupeds, studies showed that non-compressive loads play a significant role (Galbusera and Bassani, 2019).

Fig. 6 Simplified representation of the action of the body weight in quadrupeds (left) and in bipeds with a vertical spine (right). [Adapted from Galbusera and Bassani, 2019] In quadrupeds such as sheep, the body weight generates an extension load on the spine resulting in sag, whereas, in a vertical spine, body weight and muscles induce a mostly axial loading in compression.

Evolution

The Origin of Spines in Fish

The spine is an integral part of many different types of creatures; however, it is not the most common support structure, with around 90 % of animals being invertebrates (Editors of Encyclopedia Britannica, “invertebrate”). This begs the question, why is there a spine? The spine can be traced back to the Cambrian period, around 550 million years ago (CK-12 Foundation, n.d.). As can be seen in Fig. 8, a phylogenetic tree, the vertebral column can be traced back to a common ancestor: the jawless fish.

Fig. 7 A phylogenetic tree showing all Vertebrates and when they evolved. [Adapted from CK-12 Foundation, n.d.]

The first creatures to have a spine-like structure were the agnathan, or jawless fish (CK-12 Foundation, n.d.). Their bodies were supported by rudimentary vertebrae and a stiff rod called a notochord: the precursor to the backbone (Budd, 2013). The notochord was made from a cartilage-like material and was the norm for jawless fish, like modern-day hagfish. Lampreys are very similar to hagfish; except they have a slightly more evolved partial vertebral column. A comparison of two agnathan can be seen in Fig. 9. These early spines allowed for increased protection of the essential central nervous system. Furthermore, it also allowed these fish more freedom of mobility because, up to this point in time, most organisms were bottom feeders (Budd, 2013). From common ancestors very similar to these two fish, the rest of the vertebrates evolved.

Fig. 8 Simulations of the notochord of the Hagfish and Lamprey. [Adapted from “Jawless Fish” | Suny Orange, n.d.]

Around 50-100 million years later, the first full vertebral column was found with the emergence of bony fish (CK-12 Foundation, n.d.). Bony fish would evolve into modern day ray-finned and lobe- finned fish. As can be seen in Fig. 10 and 11, the skeleton of bony fish is noticeably different from that of cartilaginous fish, with the key difference being their shape. Bony fish tend to be a lot narrower than cartilaginous fish, who are shaped more like torpedoes. Each has their own advantages and disadvantages. An example would be that the cartilage is tough, but flexible enough structural support to allow this type of fish to grow quite large (CK-12 Foundation, n.d.). However, the main disadvantage of the cartilaginous spine and skeleton, is that it is much more easily damaged as cartilage is weaker than bone. Conversely, a big advantage of a bony skeleton and vertebral column is that they allow a greater variety of points of attachment, which in turn allows more a greater range of motion.

Fig. 9 The skeleton of a bony fish. [Adapted from Ramel, “Fish Skeleton 101”]
Fig. 10 Simulation of a shark skeleton. [Adapted from “Skeletal/muscular system” | The Great White Shark, n.d.]

From bony lobe-finned fish came the next step in evolution with amphibians. This evolution occurred around 365 million years ago, and it allowed amphibians to become the first land dwellers (CK-12 Foundation, n.d.). There were shortcomings, however, with amphibians having to lay their eggs in water, a trait which holds true to today with modern amphibians such as frogs, salamanders, and caecilians. The main reason for this is because the eggs are not amniotic and must therefore be laid in water to ensure they do not dry out, but also due to the fact that amphibians need to undergo metamorphosis. Amphibians are essentially born without a vertebral column. Throughout their larval stage, amphibians must ossify their centra (Carroll et al., 1999), essentially growing their vertebral column as they grow, as Fig. 12 indicates. This is another reason amphibians were not able to stray far from land, because their lack of vertebral column at early stages of life makes locomotion on land almost impossible.

Fig. 11 Frog Metamorphosis. [Adapted from Hunt, 2014]

Reptilian Spines

Around 300 million years ago, the first reptiles evolved from amphibians (CK-12 Foundation, n.d.). Reptiles had several advantages over amphibians, with their eggs being amniotic and using internal fertilization; however, a key one was the fact they were born with their vertebral column (Kusama, 1979).This allowed reptiles to move across land much more easily and allowed them to live essentially anywhere. However, the reptilian vertebrae diverged, with many different types of spines being formed. An interesting example of this is the vertebral column of the snake. The snake can have 300+ vertebrae compared to a lizard’s 65 and a mouse’s 60 (Woltering, 2012). This is due to their locomotion style of crawling and burrowing. Interestingly, there are multiple other animals who evolved convergently, such as the amphibious caecilian. As can be seen in Fig. 13, a mouse and snake, in this case a corn snake, start off similarly when embryos. However, when undergoing embryosis, the snake spine segments and, at hatching for the snake and birthing for the mouse, the number of vertebrae has dramatically changed (Woltering, 2012). This is because, at regular intervals, somites bud off from the anterior end of the presomitic mesoderm (PSM) while at its posterior end proliferation of the tail bud replenishes the population precursor cells within the PSM. This means that snakes can essentially grow a lot of vertebrae whilst not taking a long time to do so. This adaptation allowed the snake to become one of the most versatile creatures on this planet and allowed it to survive for such a long time (Woltering, 2012).

Fig. 12 (top) Skeletons of a newborn mouse and a hatching stage corn snake. (bottom) A day 12 post-fertilization mouse embryo and a ~ 2 days post ovo-positioning corn snake embryo are shown. [Adapted from Woltering, 2012]

Mammalian Spines

The next step in evolution was the mammals, who evolved around 200 million years ago (CK-12 Foundation, n.d.). Mammals evolved from reptiles and, as such, share some of the same traits. An example of this can be seen in Fig. 13, where the mouse embryo and the corn snake embryo are remarkably similar. Mammals are an interesting case when compared to other classes in that, while they differ greatly morphologically, the structure of the spine remains fairly constant. Most mammals tend to have around 26 or 27 vertebrae, which includes cervical, thoracic and lumbar vertebrae (Williams et al., 2019). There are some exceptions, for example, humans have only 24 vertebrae. It appears that this number is common because it allows for the best range in movement for quadrupeds. Conversely, humans, and other apes who are bipeds, have adapted differently due to their anti-pronograde behaviors. Furthermore, another important adaptation is that of making the back more mobile which allows for easier live birthing. Fig. 14 presents the evolution of the mammalian spine; it can be seen in the figure that the first mammals did not have four regions of the spine like modern day mammals. This is a further example of the evolution of the mammalian spine (National Science Foundation, 2018).

Fig. 13 The three stages of mammal backbone evolution on a phylogenetic tree. [Courtesy of Stephanie E. Pierce, Museum of Comparative Zoology, Harvard University. Adapted from National Science Foundation, 2018] (bottom right) Edaphosaurus; (middle left) Thrinaxodon; (top) A modern-day mouse.

Avian Spines

The last vertebrate to appear is the bird, which appeared around 150 million years ago (CK-12 Foundation, n.d.). As can be expected, the bird’s vertebral column has adapted, for the most part, for flight. One of the evolutionary traits is the lightweight bones, which allows for easier flight (McCauley, n.d.). Another key aspect is the flexibility of their cervical vertebrae, this allows birds to have a large range of motion for their head. This is important because many birds have immobile eyes. Furthermore, birds tend to have more vertebrae than mammals, which allows for increased stability in the neck, especially useful when in flight (McCauley, n.d.). A final adaptation, as can be seen in Fig. 15, of the avian spine is the fact that it has fused collarbones and keeled breastbones. These two traits are both useful for flight as they strengthen the spine against the harsh conditions. It should be noted that these characteristics also come in useful when swimming for some birds (McCauley, n.d.). However, these aspects are not common across all birds. Indeed, flightless birds have evolved slightly differently than flying ones. For example, they have stronger bones because they do not need to worry about being light enough to fly, they also do not have a keeled breastbone for the same reason (McCauley, n.d.).  

Fig. 14 Diagram of the fused collar bone and keeled sternum of a bird. [Adapted from McCauley, n.d.]  

Purpose of the Spinal Cord

The spinal cord is a vital organ in vertebrates as it acts as an extension of the brain and a highway for neurons to send information from the brain to the rest of the body. The signals from the brain are sent through the membrane potential along the axons of neurons. There are two types of signals sent: sensory and motor. Sensory signals come from the body and are sent to the brain (Highsmith, “Spinal Cord, Nerves, and the Brain”). They alert it to changes in temperature, pressure, pain, and touch. Motor signals can either be voluntary or reflex. Voluntary signals movement and come from the brain. Meanwhile, reflex signals come from the brain and cause involuntary movements of the body. These signals travel to and from the brain, into the spine and to nerve endings found throughout the body (Highsmith, “Spinal Cord, Nerves, and the Brain”). Therefore, if the spinal cord is severed, the organism will lose mobility as the connection between the brain and the body will be lost.

Fig. 15 Labelled schematic of the spinal cord. [Adapted from Nall, 2019]  

Structure and Composition of the Spinal Cord

The spinal cord is protected by the spine and is cushioned by cerebrospinal fluid. Moreover, it is composed of bundles of nerve fibers that run along the body of vertebrates. These fibers are made of a cell body, an axon covered by a myelin sheath and an axon terminal. The myelin sheath acts as an insulator for the axon and allows electrical impulses to be transmitted along the nerve cells (Lewis and Eisen, 2003). In addition, myelin is composed of two types of glial cells: in the peripheral nervous system, they are Schwann cells, and, in the central nervous system, they are oligodendrocytes (Mokalled et al., 2016). Therefore, the myelination of oligodendrocyte cells will be the focus. The latter is a recent feature in vertebrates, and it allows rapid conduction at a speed that would otherwise require large axons to be achieved (Appel and Eisen, 1998; Briona and Dorsky, 2014). Thus, making myelin is crucial in the transmission of signals in the body. In addition, the lack of a myelin sheath can cause axon degeneration (Mount and Monje, 2017). However, the interest shown is into how the myelin sheath wraps itself around the nerve’s axon.

Myelin

Synthesis of Myelin

The production of myelin begins with the production of oligodendrocyte precursor cells (OPCs) in the neural tube of the body which then migrate to the future white matter tracts of the brain. The OPCs will continue to extend and contract their processes until they reach their final destination to repulse other OPCs, thus controlling the density of these cells (Lewis and Eisen, 2003; Mokalled et al., 2016; Mount and Monje, 2017; Simons and Trotter, 2007). To ensure there are enough OPCs for the number of axons, the body will produce excess OPCs which will be eliminated if they are not myelinated to an axon. Once in their final position, the OPCs will mature and wait for a neural signal to transform from an OPC into a myelin-forming oligodendrocyte (Simons and Trotter, 2007). However, this neural signal has yet to be discovered. The OPCs do not require an adhesion molecule to initiate myelination of the axon unlike Schwann cell myelination. It is believed that the OPCs instead receive signals from the axon themselves to begin the process of myelination. Once an axon is being myelinated by an OPC, the shape and structure of the OPC is changed. The processes are transformed into flat sheets that wind along the axon to create a coil or stack of membranes. The method at which the myelin wraps the axon is believed to be that “there are two motions: the wrapping of the leading edge at the inner tongue around the axon underneath the previously deposited membrane and the lateral extension of myelin membrane layers toward the nodal regions” (Poitelon et al., 2020) as seen in Fig. 17.

Fig. 16 Schematic of how myelin wraps the axon. [Adapted from Simons and Nave, 2015]

Then, the membrane associated proteins called myelin-basic protein (MBPs) are delivered to the myelin and acts as clustering agents. This allows the myelin-membrane to form by compacting the cells. The MBPs are synthesized in the distal process which is the closest to the axon itself (Simons and Trotter, 2007). The MBP binds to two membrane surfaces and polymerizes thus biding the surfaces of the myelin bilayer (Susuki, 2010).

Fig. 17 Schematic of the synthesis of myelin. [Adapted from Simons and Trotter, 2007]

Composition of Myelin

Myelin is architecturally a very stable membrane. The myelin membrane is composed of a high percentage of lipids, fatty acids, and cholesterol and a low percentage of proteins (Poitelon et al., 2020). This ratio of composition is important because the because it helps the myelin wrap tighter around the axon. The three types of lipids present in myelin are cholesterol, phospholipids, and glycolipids (Poitelon et al., 2020; Simons and Trotter, 2007). This rare composition ensures that the lipid bilayer of myelin is stable by moving certain proteins into compartments through their channels. Cholesterol is very important in the stability of myelin as it increases its viscosity. In addition, cholesterol acts as a limiting agent since myelin cannot be synthesized without it. The main glycolipid in the myelin membrane is galactosylceramide (Poitelon et al., 2020). The latter accomplishes this by being a very hydrophobic molecule. Therefore, this molecule generates strong hydrophobic forces between the layers in the membrane, thus creating a zippering effect between the layers as it repulses the fluids outside the membrane. The major phospholipid found in the membrane is plasmalogen. It strengthens the bonds between lipid thus allowing a tighter and more compact membrane (Simons and Nave, 2015).

Fig. 18 I Diagram of a neuron. II Diagram depicting a myelinated axon. III Diagram of the myelin membrane lipid bilayer. IV The composition of the lipids in the myelin membrane. [Adapted from Poitelon et al., 2020] 

Regeneration of the Spinal Cord in Zebrafish

Mammals can do very little in respect to repairing damage that occurs to their spinal cord when it is severed, etc. This is because the scarring on the glial cells acts as an obstruction, thus causing the loss of the body’s motor abilities. However, zebrafish may regenerate their axons and remyelinate them in their adult and embryonic stages (Appel and Eisen, 1998; Lewis and Eisen, 2003). Therefore, they may repair their spinal cord after injury from slight damage to completely severing the spinal cord to almost the same level of function as before (Lewis and Eisen, 2003). This is because the glial cells in zebrafish form a bridge across the spinal cord tissue to facilitate the regrowth of the axons in the nerve tissue as seen in Fig. 20 (Mokalled et al., 2016).

Fig. 19 Depiction of how a severed zebrafish spine regenerates. [Adapted from Mokalled et al., 2016]

This phenomenon is believed to be partially due to the secretion of connective tissue growth factor a (ctgfa) after the injury occurred. CTFG is a matricellular protein that affects the signaling pathways, cell adhesion and migration of the cell (Mokalled et al., 2016). Another theory is that cells expressing a dbx1 (which is known to label multipotent progenitors in mammals) are found in the radial glial. The glial of the zebrafish continues to produce dbx1 after they leave their embryonic stage (Briona and Dorsky, 2014). The Dbx gene encodes a series of transcription factors expressed in the intermediate spinal cord. Zebrafish are known to have two Dbx1 orthologs. This gene also has exhibited the capability to create new neurons and regenerative blastema, thus indicating that dbx1 along with radial glia may be stem cells for the regeneration of the spinal cord (Briona and Dorsky, 2014).

Conclusion

Due to the spine, humans can stand up and keep upright. It allows the freedom of movement and the ability to bend easily with flexibility. Additionally, the spine is designed to protect the spinal cord (“A Patient’s Guide to Anatomy and Function of the Spine” | University of Maryland Medical Center, n.d.). The latter is contained in the spinal column and without it, any human would not be able to move any part of its body and the organs would not function.

In each vertebra, there are two nerve roots (the dorsal and the ventral) that come out of the spinal cord and connect to a single spinal nerve on each. Each nerve root conveys very specific information. The dorsal nerve root carries sensory messages such as information about touch, pressure, temperate, or even pain from our body to the brain (“Why is the spinal cord important?” | Coloplast Care, n.d.). The ventral nerve root is the efferent motor root as it carries signals from the brain destined to control motor function. It is responsible for transmitting output from the brain and spinal cord to the body’s muscles.

Most vertebrates are quadrupedal animals. However, there are some species, including humans, that walk on their two feet called bipeds. For these species, the alternated loading conditions and movement requirements subsequently led to different changes and adaptation in the structure and the design of the spine (Appel and Eisen, 1998).

The spine can be traced back to the Cambrian period. The first creatures to have a spine-like structure were the agnathan or jawless fish. Around 50-100 million years later, the first full vertebral column was found with the emergence of bony fish. From bony lobe-finned fish came the next step in evolution with amphibians. This evolution occurred around 365 million years ago, and it allowed amphibians to become the first land dwellers. The next step in evolution was mammals, who evolved around 200 million years ago. The latter evolved from reptiles and, as such, share some of the same traits. The last vertebrate to appear is the bird, which appeared around 150 million years ago (CK-12 Foundation, n.d.). As can be expected, the bird’s vertebral column has adapted, for the most part, for flight.

The spinal cord is a vital organ of vertebrates as it acts as an extension of the brain and a highway for neurons to send information from the brain to the rest of the body. What is more, the spinal cord is composed of bundles of nerve fibers that run along the body of vertebrates. Nerve fibers are made of a cell body, an axon covered by a myelin sheath, and an axon terminal. The myelin sheath acts as an insulator for the axon and allows electrical impulses to be transmitted along with the nerve cells (Lewis and Eisen, 2003). Myelin is architecturally a very stable membrane. It is composed of a high percentage of lipids, fatty acids, and cholesterol and a low percentage of proteins.

Mammals can do very little to repair the damage that occurs to their spinal cord when it is injured. This is because the scarring on the glial cells acts as an obstruction, causing the loss of the body’s motor abilities. However, zebrafish can regenerate their axons and remyelinating in their adult and embryonic stages (Appel and Eisen, 1998; Lewis and Eisen, 2003). Therefore, they can repair the spinal cord after an injury from slight damage or complete severing to almost the same level of function as before.

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