Development of the nervous system in humans
The development of the nervous system in humans, or neural development, or neurodevelopment involves the studies of embryology, developmental biology, and neuroscience. These describe the cellular and molecular mechanisms by which the complex nervous system forms in humans, develops during prenatal development, and continues to develop postnatally.
Some landmarks of neural development in the embryo include:
- The formation and differentiation of neurons from stem cell precursors
- The migration of immature neurons from their birthplaces in the embryo to their final positions.
- The outgrowth of axons from neurons and the guidance of the motile growth cone through the embryo towards postsynaptic partners.
- The generation of synapses between axons and their postsynaptic partners.
- The synaptic pruning that occurs in adolescence.
- The lifelong changes in synapses which are thought to underlie learning and memory.
- Activity-independent mechanisms. Activity-independent mechanisms are generally believed to occur as hardwired processes determined by genetic programs that are played out within individual neurons. These include differentiation, migration, and axon guidance to their initial target areas. These processes are thought of as being independent of neural activity and sensory experience.
- Activity-dependent mechanisms. Once axons reach their target areas, activity-dependent mechanisms come into play. Neural activity and sensory experience will mediate formation of new synapses, as well as synaptic plasticity, which will be responsible for refinement of the nascent neural circuits.
Development of the human brain
Overview
The central nervous system is derived from the ectoderm—the outermost tissue layer of the embryo. In the third week of human embryonic development the neuroectoderm appears and forms the neural plate along the dorsal side of the embryo. The neural plate is the source of the majority of neurons and glial cells of the CNS. A groove forms along the long axis of the neural plate and, by week four of development, the neural plate wraps in on itself to give rise to the neural tube, which is filled with cerebrospinal fluid. As the embryo develops, the anterior part of the neural tube forms three primary brain vesicles, which become the primary anatomical regions of the brain: the forebrain, midbrain, and hindbrain. These simple, early vesicles enlarge and further divide into the five secondary brain vesicles – the telencephalon, diencephalon, mesencephalon, metencephalon, and myelencephalon. The CSF-filled central chamber is continuous from the telencephalon to the spinal cord, and constitutes the developing ventricular system of the CNS. Because the neural tube gives rise to the brain and spinal cord any mutations at this stage in development can lead to fatal deformities like anencephaly or lifelong disabilities like spina bifida. During this time, the walls of the neural tube contain neural stem cells, which drive brain growth as they divide many times. Gradually some of the cells stop dividing and differentiate into neurons and glial cells, which are the main cellular components of the CNS. The newly generated neurons migrate to different parts of the developing brain to self-organize into different brain structures. Once the neurons have reached their regional positions, they extend axons and dendrites, which allow them to communicate with other neurons via synapses. Synaptic communication between neurons leads to the establishment of functional neural circuits that mediate sensory and motor processing, and underlie behavior.Neural induction
During early embryonic development the ectoderm becomes specified to give rise to the epidermis and the neural plate. The conversion of undifferentiated ectoderm to neuro-ectoderm requires signals from the mesoderm. At the onset of gastrulation presumptive mesodermal cells move through the dorsal blastopore lip and form a layer in between the endoderm and the ectoderm. These mesodermal cells that migrate along the dorsal midline give rise to a structure called the notochord. Ectodermal cells overlying the notochord develop into the neural plate in response to a diffusible signal produced by the notochord. The remainder of the ectoderm gives rise to the epidermis. The ability of the mesoderm to convert the overlying ectoderm into neural tissue is called neural induction.The neural plate folds outwards during the third week of gestation to form the neural groove. Beginning in the future neck region, the neural folds of this groove close to create the neural tube. The formation of the neural tube from the ectoderm is called neurulation. The ventral part of the neural tube is called the basal plate; the dorsal part is called the alar plate. The hollow interior is called the neural canal. By the end of the fourth week of gestation, the open ends of the neural tube, called the neuropores, close off.
A transplanted blastopore lip can convert ectoderm into neural tissue and is said to have an inductive effect. Neural inducers are molecules that can induce the expression of neural genes in ectoderm explants without inducing mesodermal genes as well. Neural induction is often studied in xenopus embryos since they have a simple body pattern and there are good markers to distinguish between neural and non-neural tissue. Examples of neural inducers are the molecules noggin and chordin.
When embryonic ectodermal cells are cultured at low density in the absence of mesodermal cells they undergo neural differentiation, suggesting that neural differentiation is the default fate of ectodermal cells. In explant cultures the same cells differentiate into epidermis. This is due to the action of BMP4 that induces ectodermal cultures to differentiate into epidermis. During neural induction, noggin and chordin are produced by the dorsal mesoderm and diffuse into the overlying ectoderm to inhibit the activity of BMP4. This inhibition of BMP4 causes the cells to differentiate into neural cells. Inhibition of TGF-β and BMP signaling can efficiently induce neural tissue from human pluripotent stem cells, a model of early human development.
The early brain
Late in the fourth week, the superior part of the neural tube flexes at the level of the future midbrain—the mesencephalon. Above the mesencephalon is the prosencephalon and beneath it is the rhombencephalon. The optical vesicle forms at the basal plate of the prosencephalon.The spinal cord forms from the lower part of the neural tube. The wall of the neural tube consists of neuroepithelial cells, which differentiate into neuroblasts, forming the mantle layer. Nerve fibers emerge from these neuroblasts to form the marginal layer. The ventral part of the mantle layer forms the motor areas of the spinal cord, whilst the dorsal part forms the sensory areas. Between the basal and alar plates is an intermediate layer that contains neurons of the autonomic nervous system.
In the fifth week, the alar plate of the prosencephalon expands to form the cerebral hemispheres. The basal plate becomes the diencephalon.
The diencephalon, mesencephalon and rhombencephalon constitute the brain stem of the embryo. It continues to flex at the mesencephalon. The rhombencephalon folds posteriorly, which causes its alar plate to flare and form the fourth ventricle of the brain. The pons and the cerebellum form in the upper part of the rhombencephalon, whilst the medulla oblongata forms in the lower part.