Growth and Differentiation of the Nervous System

Growth and Differentiation of the Nervous System

The nervous system is formed of specialized cells called neurons that use electrical and chemical signals to carry information to and away from the brain. Neurons contact each other, and other tissues, at a specialized region of the cell called a synapse. There, chemicals called neurotransmitters are released by one neuron and received by the other. Long, thin regions of the neuron that carry information from a distant location to the neuronal cell body are called axons and dendrites. Neurons connect to, or inner-vate, every type of tissue in the body, including bones, skin, organs, and muscles. The information they carry allows organisms to sense the world, think, react, and maintain body function. Normal growth and development of the nervous system is necessary for forming a normal organism.

Genetic Basis of Development

Many of the accepted underlying mechanisms for nervous system development were discovered through research on organisms such as the frog, the fruit fly, and the nematode worm. The results of this research are valid even for human development because of a type of gene called the Hox genes. These genes are remarkably similar in nearly all animals, as well as plants and yeast. This is because they are so important for development in all forms of life that they have not changed very much throughout the course of evolution. Hox genes encode proteins that are expressed in different combinations and locations of the embryo. The balance of Hox gene products is so fundamental for development that, by manipulating the amount and location of the Hox proteins, developmental biologists were able to observe improper development of body parts, and misplaced, multiple, or backward limbs in animals such as frogs, chickens, and fruit flies.

Hox genes are responsible for organizing development of the portion of neural tube located within the trunk and limbs of the embryo. Segmentation of internal tissues is an evolutionary remnant from distant ancestors that had clear segmentation, such as earthworms. Thus, in the human embryo, motor and sensory neurons, as well as muscle and bone, are organized into discrete sections called embryological somites. The size and location of somites are defined by the extent and location of Hox gene transcription. Somites become functional units in the adult, such that each region contains neurons from the same part of the spinal cord.

Differentiation of the Nervous System

The vertebrate nervous system arises from ectodermal tissue of the embryo, which also gives rise to the skin. All ectoderm cells have the ability to develop into neural tissue and skin, but only those cells that are adjacent to the notochord do so. The notochord is an elongated, tubelike structure that runs down the midline of the embryo, underneath what will become the spinal cord. At the stage when the embryo is still only a sack of cells (gastrula stage), the notochord forms and releases chemicals onto the overlying ectoderm, causing those cells to differentiate into neurons. Differentiation is the process by which an embryonic precursor cell develops into a specialized mature cell. The first step in the differentiation of the nervous system is the formation of a flat strip of cells called the neural plate. This structure is formed from rapidly dividing ectoderm cells. In the second step, the continued propagation of these cells forces the sides of the plate to curve upward into a neural fold, and then in the third step, the ends fuse into a neural tube. The neural tube lies above the notochord, and it will eventually give rise to all the nervous tissue in the body, including sensory neurons in toes and fingers, the spinal cord, optic neurons from the eye, and the brain. In the fourth step, ectodermal cells on either side of the neural tube grow over and shield the neural tube from the external environment, eventually becoming the skin that will overlie the spinal cord. In a rare congenital disease called spina bifida, this skin fails to fuse, and the baby will be born with its spinal cord exposed. When the neural tube is covered, also in the fourth step, a group of cells called neural crest cells migrates out of the neural tube and travels to different parts of the developing embryo. These cells will develop into facial bones, dentine-producing cells (for teeth), the tissue covering the brain, and glial cells, neuronal support cells, in the peripheral nervous system.

The differentiation of the neural tube is most clearly illustrated by one of the best-known differentiation-inducing chemicals from the notochord, named sonic hedgehog after a Nintendo video game character. Sonic hedgehog is released from the dorsal (toward the back) notochord, and induces a specialized region of the neural tube called the floorplate. The roofplate then develops across from the floorplate at the ventral (toward the front) region, and begins to produce a different differentiating chemical called bone morphogenic protein (BMP). BMP is a completely different molecule than sonic hedgehog and it causes cells to differentiate into a different type of neuron. Large amounts of sonic hedgehog in the local environment of a cell cause it to develop into a motor (muscle-related) neuron, whereas a relatively high concentration of BMP causes differentiation into sensory (touch, temperature, and pain) neurons. This organization persists into adulthood, so that the ventral half of the spinal cord always contains sensory neurons and the dorsal half always contains motor neurons.

The portion of the neural tube located in the embryo's head uses some of the same chemical signals as the spinal cord, but differentiation occurs in a much different manner. Here, the neural tube will form into the brain. First, the tube forms into three distinct regions: the hindbrain, midbrain, and forebrain. Later, these regions specialize into the unique divisions of the mature brain. The hindbrain is very important in development because its sides swell into structures called rhombomeres, which exist only in the embryo. Rhombomeres are fundamental organizing centers because they release many chemicals that tell other parts of the neural tube how to differentiate. In the midbrain, specialized cells called isthmus cells release chemicals that establish an anterior-posterior axis. These chemicals tell cells that are located more anterior (nearer to the top of the head) to develop in a different way from those that are located more posterior (nearer to the spinal cord).

Development of the forebrain is very complex, but it is also mediated by the production of certain inducing chemical factors. Furthermore, development is shaped by the speed of cell division, meaning that regions that grow cells more quickly will be larger in the adult organism. Another means of controlling brain development is through cell migration. Many undifferentiated pre-neuronal cells are "born" near the ventricles, fluid-filled spaces located in the center of the brain, and then migrate to another region. The order of cell generations (i.e., born first, second, third, etc.) will determine what kind of neuron it will differentiate into and where it will eventually settle.

Growth of the Nervous System

As neurons mature, they grow dendrites and axons toward other cells. When dendrites and axons encounter the appropriate target cell, they will form synapses that may last for the life of the organism. Neuronal migration and growth are partly dependent on chemical guidance cues from the tissues through which they grow, and partly on specialized support cells that provide a framework along which migrating neurons can travel. One example of this migration is a sensory neuron in a seven-foot-tall person: the sensory neuron has its cell body in the spinal cord but must extend an axon to the big toe nearly three-and-a-half feet away. Chemicals in the back, thigh, leg, and foot tell the neuron in which direction to grow. Once a synapse is formed between two neurons, or between a motor neuron and a muscle fiber, the target cell releases a chemical trophic factor that sustains the synapse and the survival of the presynaptic neuron. Trophic factors keep the synapse alive and functional, but if the target cell stopped producing them the synapse would disintegrate.

Animals such as humans that are born helpless and underdeveloped do not achieve fully mature nervous systems until sexual maturity. During their first few years of life, human babies have very poor coordination, strength, perception, and cognitive abilities because their nervous system is still forming interconnections. Babies are therefore physically incapable of seeing, feeling, and understanding the world in the same manner as adults. This is one explanation for why memories from early childhood are cloudy and incomplete.

Brain growth after birth occurs by a great increase in the number of neurons and the number of synapses. However, many of these cells and many synapses die off before maturity. This is because the vertebrate method of development uses excess neurons for the embryo to accommodate environmental differences and the possibility of an accident. If the excess neurons are needed, they become active, and if active they will survive. If the neurons remain inactive, they will die. This process is inherent in the development of many organisms, even the human. Thus, if a baby is exposed to many bright colors, variable sounds, and interesting sensations, neurons in its brain will be very active and will survive. If the same baby is hidden from bright colors, hears few sounds, and is given no tactile stimulation, many of these neurons will die because they are not being used at an early age. Later in life, the baby in the first situation will be better able to interpret and understand the world than the baby in the second situation.

This example of neuron cell death illustrates critical periods in development. A critical period is a specific length of time in an organism's youth in which it is possible to save neurons from cell death. If the correct stimuli are not presented before the end of the critical period, that individual will never acquire normal abilities. The correct stimulus for a sensory neuron, for example, is touch, and the correct stimulus for a visual neuron is vision. One demonstration of this effect is manipulation of the visual system of the cat. If a kitten's eyes are covered between ten and twenty days after birth, the kitten will be blind for the rest of its life, even after the patches are removed. Human language, vision, hearing, and learning ability all have critical periods. These have been revealed through rare circumstances of neglect in which children are denied exposure to language and/or visual stimuli and tactile stimulation. Psychologists who studied these examples found that, after a certain age, children who have not had access to language or culture are not able to learn how to speak or interact with other humans in a normal manner.

see also Nervous System.

Rebecca M. Steinberg

Bibliography

Hopkins, W. G., and M. C. Brown. Development of Nerve Cells and Their Connections. New York: Cambridge University Press, 1984.

Le Douarin, Nicole, and Chaya Kalcheim. The Neural Crest. Cambridge, U.K.: Cambridge University Press, 1999.

Rymer, Russ. Genie: A Scientific Tragedy. New York: Harper Perennial, 1994.

Spitzer, Nicholas C. Neuronal Development. New York: Plenum Press, 1982.

Stein, Donald G. Development and Plasticity in the CNS: Organismic and Environmental Influences. Worcester, MA: Clark University Press, 1988.