DEVELOPMENT OF THE BRAIN, SPINAL CORD AND NERVES
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 the Brain
The cephalic neural tube by the 4th week of development, has three enlargements. These enlargements are called the: prosencephalon (forebrain), mesencephalon (midbrain) and the rhombencephalon (hindbrain). During the next week the prosencephalon enlarges and lateral extensions appear. These lateral extensions are the telencephalon and they are connected by a midline structure called the diencephalon. The mesencephalon remains as a single structure. The rhombencephalon then develops two enlargements and these are the metencephalon and the myelencephalon.
As these enlargements appear, the brain begins to curve in certain areas. There is a cephalic flexure that appears in the region of the midbrain or mesencephalon. The pontine flexure is located at the junction between the metencephalon and the mylencephalon. It will eventually give rise to the rhombic lip of the metencephalic alar plate and then become the cerebellum. There is also a cervical flexure that appears at the medulla-spinal cord junction.
The internal central canal of the neural tube in the region of the brain enlarges and except for the midbrain develops into ventricles. The ventricles will contain the cerebrospinal fluid.
A description of each of the regions of the brain will follow. In addition, you will learn the development of the cranial nerves of each region of the brain. In thinking about the brain you should keep in mind the concept of cell columns -- groups of neuronal cell bodies or nuclei that extend throughout a length of the spinal cord. The ventral horn cells of the spinal cord constitute a cell column that runs the length of the cord, and contains somatic efferent neurons that are involved in motor innervation to skeletal muscles. Sensory neurons of the spinal cord form cell columns in the dorsal horn of the spinal cord. Finally, autonomic motor neurons form a cell column that is located in the lateral gray horn and is located from T1 to L2(3).
Development of the Mylencephalon
The mylencephalon develops into the medulla. The caudal end of the mylencephalon remains closed with a central canal continuous with the central canal of the spinal cord. As the more cephalic end of the medulla is reached, the roof of the ventricle opens and is drawn out as the roof plate. Together with the pia the roof plate gives rise to the tela choroidea. Heavily vascularized parts of the tela choroidea project into the 4th ventricle as the choroid plexus.
The low medulla contains a central canal and the cell columns that develop are for the hypoglossal nerve (CN12), the vagus nerve (CN10) and the sensory nuclei for the sensory nuclei for cranial nerves 10 and 5 (the trigemminal nerve). New pathways that ascend and descend through the spinal cord are located posterior and lateral in the low medulla.
The high medulla see some changes. As mentioned above the fourth ventricle opens. Cell columns for the vestibular nuclei and the cochlear nuclei appear. The sensory nuclei for cranial nerve nuclei 5, 9 (glossopharyngeal nerve) and 10 also are found. Motor nuclei for the glossopharyngeal and vagus nerves as well as the 12th cranial nerve are also present. The long ascending and descending tracts have assumed a more anterior and lateral position.
Development of the Metencephalon
The metencephalon develops into the cerebellum and the pons. The cephalic part of the fourth ventricle continues into the pons. The roof plate becomes the superior medullary velum a region of the pons that will be covered by the cerebellum. During the formation of the cerebellum the mantle layer of the rhombic lip will develop into the deep nuclei of the cerebellum. It will also give rise to the cells that will form the cerebellar cortex.
The cell columns of the pons include those for the sensory nuclei for the vestibulocochlear nerve, the trigemminal nerve, the facial nerve and the motor nuclei for the facial nerve, the trigemminal nerve and the abducens nerve. Descending pathways are located in the base of the pons along with pontine nuclei. Other ascending pathways are located in the anterolateral pons, and the middle and superior cerebellar peduncles.
Development of the Mesencephalon
The mesencephalon changes very little during development. The central canal is small and is now called the cerebral aquaduct. The roof plate and the alar plate becomes the tectum and contains nuclei associated with vision and with hearing. The floor and the basal plates become the cerebral peduncles.
The cell columns associated with the midbrain include those associated with the eye muscles as well as with autonomic function. The newer ascending and descending pathways are found along the anterolateral tegmentum and crus cerebri portions of the midbrain.
Development of the Diencephalon
This part of the brain develops into the thalamus, the epithalamus, the subthalamus and the hypothalamus. The central canal forms the third ventricle. The roof plate forms the this tela choroidea and choroid plexus and is continuous with the lateral ventricle via the interventricular foramina (of Monroe).
The diencephalon does not have a basal plate. The alar plate divides into a dorsal region and a ventral region and the dividing line is the hypothalamic sulcus. The thalamus is located in the dorsal region and constitutes a major set of relay nuclei for pathways involved in sensory function. The ventral region is comprised of hypothalamic nuclei. These nuclei are involved in the regulation of visceral function.
The pituitary gland develops in part from a downward growth of the diencephalon. This is called the infundibulum. The infundibulum gives rise to the pituitary stalk, and the pars nervosa of the pituitary gland. The remainder of the pituitary gland arises from ectoderm from the stomodeum, that portion of ectoderm immediately in front of the oral plate. This ectoderm is called Rathkes pouch. This ectoderm tissue gives rise to the pars distalis and the pars tuberalis of the pituitary gland.
Development of the Telencephalon
During development the telencephalon expands significantly. During their development they flex into a "C-shaped" structure. The mantle layer gives rise to the cells of the basal ganglia a region of the brain that regulates motor function. The mantle layer also gives rise to cells that will migrate into the marginal layer and these cells become the cortical gray cells. During development the medial walls of the telencephalon fuse with the lateral walls of the diencephalon. The internal capsule forms at the line of fusion. The growth of the telencephalic hemispheres causes them to grow over the basal ganglia and the cortex over it called the insular cortex. The central canal of the telencephalon forms the lateral ventricle. The choroid plexus develops along the medial wall of the lateral ventricle. A corpus callosum forms as a group of fibers that connect one hemisphere to the other.
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
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