Reading: Langmans Medical Embryology Chapter 20
1. Development of the Spinal Cord and Nerves
Entering the third week the ectoderm overlying the notochord thickens and forms the neural plate. The neural plate changes shape in the following days as it begins to fold and the lateral edges begin to come to the midline. At this time the neural plate is described as consisting of two neural folds. The neural folds meet in the midline and at this point a neural tube is formed. The neural tube first occurs in the cervical region and the fusion of the neural folds proceeds both cephalically and caudally. In addition to the formation of the neural tube, a group of cells at the junction of the neural plate and the remaining ectoderm also differentiate and become located lateral and dorsal to the neural tube. This cluster of cells is call the neural crest.
The wall of the neural tube is made up of neural ectodermal cells that are called the neuroepithelium. These neuroepithelial cells surround a central canal. The neural epithelial cells give rise to a second population of cells called neuroblasts. The neuroblasts form a peripheral layer around the neuroepithelial cells that is called the mantle layer. This layer of cells will form the gray matter of the spinal cord. Neuronal processes from the neuroblasts extend peripherally from the mantle layer and the collection of these fibers form the marginal layer. As these fibers become myelinated, they go on to form the white matter of the spinal cord. Neuroepithelial cells also differentiate into spongioblasts (gliablasts). The spongioblasts will develop into the supportive cells or neuroglia found in the central nervous system. Neuroglial cells include ependymal cells, fibrous and protoplasmic astrocytes and oligodendroglia.
The neural tube in cross section has a diamond shaped central canal. The lateral corners of the diamond are actually a sulcus that is called the sulcus limitans. This sulcus represents the dividing line between the more dorsally located cells of the neural tube that form the alar plate, and the more ventrally located cells of the neural tube that are called the basal plate. The cells found in the alar plate are involved with sensory nerve function. The cells found in the basal plate are involved mainly with motor function. As development continues the region between the alar plate and the basal plate forms an intermediolateral portion of the gray matter, and these neurons, will be involved in autonomic function.
Neural crest cells comprise a column of cells located dorsolateral to the neural tube. The cells will divide into segments that correspond to somites that develop in the mesoderm. Neural crest cells will develop into sensory neurons, and autonomic neurons. Neural crest cells will also give rise to the supportive cells of the peripheral nervous system, in particular the Schwann (neurolemma) cells that produce the myelin covering over peripheral axons and dendrites. Finally neural crest cells also give rise to pigment in the skin, the suprarenal medulla, some of the aorticopulmonary septum, and some cartilage of the face.
As the nervous system develops the spinal cord arranges into segments from which emerge paired dorsal and ventral roots. The ventral roots contain two types of motor neurons. The first is a somatic efferent neuron. These cells are located in the anterior horn of the gray matter, and traverse the ventral root to reach the spinal nerve. From there the fibers pass into either the dorsal or ventral rami to innervate skeletal muscle. The second type of motor fiber is the visceral efferent neuron. The cells bodies of these neurons are located in the intermediolateral portion of the gray matter and the fibers that exit the spinal cord are called preganglionic fibers. These neurons exit the spinal cord from the ventral root and the spinal nerve. From there they travel through a communicating ramus to the sympathetic chain. The preganglionic neurons either synapse in the sympathetic chain ganglia or else in other autonomic ganglia located in the abdomen and pelvis. From there the postganglionic fibers go on to innervate visceral structures. These visceral structures include smooth muscle, cardiac muscle and glands.
Dorsal roots also contain two types of neurons and these are both sensory neurons. The cell bodies of these neurons are located in the dorsal root ganglia. Some of these fibers arise from viscera and these are called visceral afferent neurons. A second group arise from somatic structures and these include skeletal muscles, skin and tendons. These are called somatic afferent neurons. The central process from these neurons enter the spinal cord via dorsal roots. These fibers synapse in the sensory portion of the gray matter that was derived from the alar plate.
Thus the spinal nerve contains four types of neurons. The four types are: 1. somatic afferent neurons; 2. somatic efferent neurons; 3. visceral afferent neurons; and 4 visceral efferent neurons. Since spinal nerves divide into dorsal and ventral rami, it is also important to recognize that the dorsal and ventral rami also contain all four neuronal fiber types.
When considering the autonomic nervous system it is important to understand that it is that part of the peripheral nervous system that innervates visceral structures. The autonomic nervous system is comprised of a two neuron chain for the motor neurons. The two neurons are 1. preganglionic neurons that come from either the intermediolateral gray of the spinal cord or from neurons that arise in the brain stem. 2. Neurons that arise in autonomic ganglia of the visceral and cranial nerves and these neurons go directly to the viscera. The sensory fibers then carry the sensory information back to the spinal cord via visceral afferent neurons.
2. Development of Muscles
By the beginning of the third week of gestation the primitive streak gives rise to the intraembryonic mesoderm. This mesoderm is located between general surface ectoderm and endoderm. In the midline, the notochord is located between the endoderm and neural ectoderm. During the next stage of development the mesoderm next to the notochord thickens and develops into the paraxial mesoderm. This paraxial mesoderm will continue to differentiate into 42 - 44 paired segments that are known as the somites. These somites develop in a cephalocaudal direction and eventually there will be 4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 8 - 10 coccygeal somites. The individual somites each differentiate further into three portions. A ventromedial portion is called the sclerotome. The sclerotome will give rise to skeletal structures such as bone and ribs. A dorsomedial portion will develop into the myotome. The myotome will form the skeletal muscles. Finally the most dorsolateral portion is called the dermatome. The dermatome will give rise to the dermis of the skin and the subcutaneous tissue.
The differentiation of the myotome includes a stage where the cells are loosely arranged into what is called the mesenchyme. Mesenchymal cells are stellate cells that are embedded in a semifluid intercellular substance. Mesenchymal cells develop into both muscle cells and connective tissue cells, and therefore are also found within the sclerotome. Those mesenchymal cells that will develop into muscle elongate and become spindle shaped, multinucleated cells that contain peripherally located myofibrils. These cells are called myoblasts. As development continues the nuclei of these cells migrate peripherally and most of the central cytoplasm becomes filled with myofibrils.
Muscle development is largely controlled by the connective tissue that surrounds these cells. For example, myoblasts in the head are surrounded by mesenchymal cells derived from neural crest. In the cervical and occipital region, the mesenchymal cells are derived from somitic mesoderm. In the rest of the body the mesenchymal cells are derived from somatic mesoderm. The development of the head muscles will be covered in the lectures on the branchial arches.
Myotomes from somites enlarge in both the dorsal and ventral directions as the myoblasts proliferate. These myotomes become divided into a dorsal epaxial and a ventrolateral hypaxial portion during development. Each myotome is innervated by a corresponding spinal nerve and the epaxial and hypaxial portions of the myotome are innervated by the dorsal and ventral rami of the spinal nerve, respectively. In the interval between the epaxial and hypaxial segments of the myotome grows the transverse processes from the vertebrae. The epaxial muscle will develop into the deep muscles of the back, while the hypaxial muscles will develop into the anterior and lateral body wall muscles.
There are five processes that can lead to the formation of a muscle. 1. In some cases, such as the rhomboideus muscles, the direction of the muscle is altered. 2. Another process that can occur is the fusion of segments of successive myotomes in the formation of a single muscle, such as the erector spinae muscle. 3. A third example is the latissimus dorsi, where muscles migrate long distances from where they originate. In these instances the nerves reflect the path of migration of the muscle. 4. In other cases, a myotome can split into more than one muscle. An example of this would be the formation of the trapezius and the sternocleidomastoid. 5. Finally, there can be degeneration of parts of the muscle with the conversion of the degenerated portions into connective tissue. An example of this is the superior and inferior posterior serratus muscles. Often a combination of these processes can occur with the migration of muscles with splitting and fusion of segments of various muscles.
3. Development of Vertebrae and Ribs
The development of cartilage and bone is discussed in the histology course. The basic steps that take place in the formation of bone are: 1. the mesenchymal cells differentiating and migrating from the sclerotome to the region of the presumptive vertebrae and ribs; 2. mesenchymal cells round up and form a precartilage mass that will then 3. take the shape of the cartilage to be formed; and finally 4. the formation of the bone by the replacement of the cartilaginous model with bone tissue.
During the fourth week of development the mesenchymal cells in the sclerotome begin to move toward the region of the notochord. As the cells migrate toward the midline the caudal half of the sclerotome moves caudally to fuse with the cranially moving cranial half of the sclerotome located below. The vertebra will then be formed from the union of cells from two adjacent sclerotomes. Therefore, in the cervical region the 8 somites form only 7 vertebrae because the cranial half of the first sclerotome fuses with the cranial mesenchymal tissue to form the occipital bone. The caudal half of the first sclerotome fuses with the cranial half of the 2nd sclerotome to form the first vertebra. The caudal half of the second vertebra fuses with the cranial half of the third vertebra to form the second vertebra. This pattern continues until the caudal part of the 8th sclerotome fuses with the cranial portion of the first thoracic sclerotome to form the first thoracic vertebra. Since there are still 8 somites, there will be an 8th myotome and an 8th cervical spinal nerve. The first seven cervical spinal nerves emerge above the corresponding vertebra. However, the 8th cervical spinal nerve now emerges above the 1st thoracic vertebra and therefore the remaining spinal nerves will emerge below the corresponding vertebra.
The migration of the sclerotome tissue toward the midline includes the growth of this tissue dorsally to form the neural arches. This tissue also gives rise to the rib primordia. In the interval between the developing vertebrae the tissue will form around the degenerating notochord. The tissue around the notochord will form the annulus fibrosus portion of the intervertebral disc. The degenerating notochord will be found as the center of the disc, the nucleus pulposus.
Since the myotomes do not migrate with the sclerotomes, the dorsal muscle will span the adjacent vertebrae. The original intersegmental arteries that were located between the somites, now come to lie in the middle of the developing vertebra.
The development of the vertebrae continues with the mesenchymal cells, which have migrated to form the precartilaginous mass, forming chondrification centers. The chondrification centers develop laterally on either side of the notochord within the vertebral bodies. Chondrification centers also develop in the lateral portions of the neural arch. These centers grow together and fuse to form the cartilaginous mass of the vertebra. Next ossification centers develop both dorsally and ventrally within the cartilaginous vertebral body. Ossification centers also develop on either side of the neural arch and in the ribs. The rib primordia give rise to the ribs and to parts of the transverse processes of the cervical vertebrae, the transverse processes of the lumbar vertebrae and the alae of the sacrum.
During the development of the vertebra and the spinal cord, each of these structures grows at a different rate during different times of development. At the 3rd month of development the length of the spinal cord equals that of the vertebral column. The spinal nerves and the relationship of the spinal nerves to the vertebra are established. Therefore the spinal cord segment is at the same level as the corresponding vertebral level. Subsequently, the spinal cord does not grow as fast as the vertebral column. The consequence of this differential growth is that the caudal end of the spinal cord lies opposite higher vertebral levels. The fact that the spinal nerves are fixed in their course of exit through intervertebral foramina, means that these nerves must descend through the vertebral canal for longer distances. At birth the lower end of the spinal cord lies opposite the 3rd lumbar vertebra. The adult position of the spinal cord is opposite the intervertebral disc between L1 and L2. This level is reached by the age of 5.
There are defects that occur in the dorsal region of the spinal cord and vertebra called spina bifida. These types of defects involve the failure of the neural arch to fuse and form a vertebral canal. When this is the only defect it is called spina bifida occulta, it usually occurs in the L5, S1 vertebral region, and it does not produce any clinical problems. At times the deformation includes the protrusion of the meninges and the subarachnoid space through the vertebral arch defect. This defect is called spina bifida with meningocele. This may or may not include spinal cord abnormalities, but the spinal cord and the spinal nerves remain in their proper position. A more severe defect occurs when the spinal cord and spinal nerves are displaced with the meninges and the cerebrospinal fluid through this neural arch defect. This is called spina bifida with meningomyelocele. Finally, the most severe case of spina bifida occurs when there is failure of neural tube fusion. This leaves an exposed area of nervous tissue (neural plate) without overlying vertebral arch or skin. This is called spina bifida with myeloschisis.
Other Web Resources
The Pediatric Pathology Index: Look specifically for the pictures of meningomyelocele.
for People with Spina Bifida or Hydrocephalus home page, and click on the "Facts about SB" button on the top of the page.
What is spinal bifida?
Association for Spina Bifida and Hydrocephalus