development of the nervous system in humans 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 to describe the cellular and molecular mechanisms by which the complex nervous system forms in humans, develops during prenatal development, and continues to develop postnatally. this article is about the development of the nervous system in humans. for information on the development of the nervous system in general, see development of the nervous system. this article is part of a series on thedevelopment of organ systems nervous systemdigestive systemreproductive systemurinary systemendocrine systemhuman developmentcirculatory system some landmarks of neural development in the embryo include the formation and differentiation of neurons from stem cell precursors (neurogenesis); the migration of immature neurons from their birthplaces in the embryo to their final positions; the outgrowth of axons from neurons and guidance of the motile growth cone through the embryo towards postsynaptic partners, the generation of synapses between these axons and their postsynaptic partners, the synaptic pruning that occurs in adolescence, and finally the lifelong changes in synapses which are thought to underlie learning and memory. typically, these neurodevelopmental processes can be broadly divided into two classes: activity-independent mechanisms and activity-dependent mechanisms. activity-independent mechanisms are generally believed to occur as hardwired processes determined by genetic programs 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. 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 further information: human embryonic development and human brain § development highly schematic flowchart of human brain development. overview the central nervous system (cns) 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 (csf). 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 (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon). these simple, early vesicles enlarge and further divide into the five secondary brain vesicles – the telencephalon (future cerebral cortex and basal ganglia), diencephalon (future thalamus and hypothalamus), mesencephalon (future colliculi), metencephalon (future pons and cerebellum), and myelencephalon (future medulla). 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 (skin) 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 (skin). 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 (express neural genes), suggesting that neural differentiation is the default fate of ectodermal cells. in explant cultures (which allow direct cell-cell interactions) the same cells differentiate into epidermis. this is due to the action of bmp4 (a tgf-β family protein) that induces ectodermal cultures to differentiate into epidermis. during neural induction, noggin and chordin are produced by the dorsal mesoderm (notochord) 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 (bone morphogenetic protein) 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 (future forebrain) and beneath it is the rhombencephalon (future hindbrain). the optical vesicle (which will eventually become the optic nerve, retina and iris) 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 (the gray matter). nerve fibers emerge from these neuroblasts to form the marginal layer (the white matter). the ventral part of the mantle layer (the basal plates) forms the motor areas of the spinal cord, whilst the dorsal part (the alar plates) 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 telencephalon). 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. the embryo's brain at four weeks. cross-section of a developing spinal cord at four weeks. the embryo's nervous system at six weeks. neuroimaging neuroimaging is responsible for great advancements in understanding how the brain develops. eeg and erp are effective imaging processes used mainly on babies and young children since they are more gentle. infants are generally tested with fnirs. the mri and fmri are widely used for research on the brain due to the quality of images and analysis possible from them. magnetic resonance imaging mri's are helpful in analyzing many aspects of the brain. the magnetization-transfer ratio (mtr) measures integrity using magnetization. fractional anisotropy (fa) measures organization using the diffusion of water molecules. additionally, mean diffusivity (md) measures the strength of white matter tracts. structural magnetic resonance imaging using structural mri, quantitative assessment of a number of developmental processes can be carried out including defining growth patterns, and characterizing the sequence of myelination. these data complement evidence from diffusion tensor imaging (dti) studies that have been widely used to investigate the development of white matter. functional magnetic resonance imaging fmri's test mentalising which is the theory of the mind by activating a network. the posterior superior temporal sulcus (psts) and temporo-parietal junction (tpj) are helpful in predicting movement. in adults, the right psts showed greater response than the same region in adolescents when tested on intentional causality. these regions were also activated during the "mind in the eyes" exercise where emotion must be judged based on different images of eyes. another key region is the anterior temporal cortex (atc) in the posterior region. in adults, the left atc showed greater response than the same region in adolescents when tested on emotional tests of mentalising. finally, the medial prefrontal cortex (mpfc) and the anterior dorsal mpfc (dmpfc) are activated when the mind is stimulated by psychology. three-dimensional sonography higher resolution imaging has allowed three-dimensional ultrasound to help identify human brain development during the embryonic stages. studies report that three primary structures are formed in the sixth gestational week. these are the forebrain, the midbrain, and the hindbrain, also known as the prosencephalon, mesencephalon, and the rhombencephalon respectively. five secondary structures from these in the seventh gestational week. these are the telencephalon, diencephalon, mesencephalon, metencephalon, and myelencephalon which later become the lateral ventricles, third ventricles, aqueduct, and upper and lower parts of the fourth ventricle from the telencephalon to the myelencephalon, during adulthood. 3d ultrasound imaging allows in-vivo depictions of ideal brain development which can help tp recognize irregularities during gestation. white matter development using mri, studies showed that while white matter increases from childhood (~9 years) to adolescence (~14 years), grey matter decreases. this was observed primarily in the frontal and parietal cortices. theories as to why this occurs vary. one thought is that the intracortical myelination paired with increased axonal calibre increases the volume of white matter tissue. another is that synaptic reorganization occurs from proliferation and then pruning. grey matter development the rise and fall of the volume of grey matter in the frontal and parietal lobes peaked at ~12 years of age. the peak for the temporal lobes was ~17 years with the superior temporal cortex being last to mature. the sensory and motor regions matured first after which the rest of the cortex developed. this was characterized by loss of grey matter and it occurred from the posterior to the anterior region. this loss of grey matter and increase of white matter may occur throughout a lifetime though the more robust changes occur from childhood to adolescence. neuronal migration neuronal migration is the method by which neurons travel from their origin or birthplace to their final position in the brain. their most common means of migration are radial and tangential migration. radial migration neural stem cells proliferate in the ventricular zone of the developing neocortex. the first postmitotic cells to migrate from the preplate which are destined to become cajal–retzius cells and subplate neurons. these cells do so by somal translocation. neurons migrating with this mode of locomotion are bipolar and attach the leading edge of the process to the pia. the soma is then transported to the pial surface by nucleokenisis, a process by which a microtubule "cage" around the nucleus elongates and contracts in association with the centrosome to guide the nucleus to its final destination. radial fibres (also known as radial glia) can translocate to the cortical plate and differentiate either