Neural development in humans
Encyclopedia
The study of neural development draws on both neuroscience
and developmental biology
to describe the cellular and molecular mechanisms by which complex nervous system
s emerge during embryonic development
and throughout life.
Some landmarks of embryo
nic neural development include the birth and differentiation
of neuron
s from stem cell precursors, the migration
of immature neurons from their birthplaces in the embryo to their final positions, outgrowth of axon
s from neurons and guidance
of the motile growth cone
through the embryo towards postsynaptic partners, the generation of synapse
s between these axons and their postsynaptic partners, the neuron 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 axon
s 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.
Neurulation is the formation of the neural tube
from the ectoderm
of the embryo. It follows gastrulation
in all vertebrates.
During gastrulation cells migrate to the interior of embryo, forming three germ layer
s— the endoderm (the deepest layer), mesoderm and ectoderm (the surface layer)—from which all tissues and organs will arise. In a simplified way, it can be said that the ectoderm gives rise to skin
and nervous system, the endoderm to the guts
and the mesoderm to the rest of the organs.
After gastrulation the notochord
—a flexible, rod-shaped body that runs along the back of the embryo—has been formed from the mesoderm. During the third week of gestation the notochord sends signals to the overlying ectoderm, inducing it to become neuroectoderm. This results in a strip of neuronal stem cells that runs along the back of the fetus. This strip is called the neural plate
, and is the origin of the entire nervous system. The neural plate folds outwards to form the neural groove
. Beginning in the future neck region, the neural folds
of this groove close to create the neural tube
(this form of neurulation is called primary neuralation). The anterior (front) part of the neural tube is called the basal plate
; the posterior (rear) 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 (the neuropores) close off.
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.
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.
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.
Neuronal migration
is the method by which neurons travel from their origin or birth place to their final position in the brain. There are several ways they can do this, e.g. by radial migration or tangential migration.
. The first postmitotic
cells to migrate form 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 into astrocyte
s or neuron
s. Somal translocation can occur at any time during development.
Subsequent waves of neurons split the preplate by migrating along radial glia
l fibres to form the cortical plate. Each wave of migrating cells travel past their predecessors forming layers in an inside-out manner, meaning that the youngest neurons are the closest to the surface. It is estimated that glial guided migration represents 80-90% of migrating neurons.
s necessary for cellular maintenance and growth by their specificity; each neurotrophic factor promotes the survival of only certain kinds of neurons during a particular stage of their development. In addition, it had been argued that neurotropihic factors are involved in many other aspects of neuronal development ranging from axonal guidance to regulation of neurotransmitter synthesis.
, generation of new neuron
s, glia, axon
s, myelin
or synapse
s. Neuroregeneration differs between the peripheral nervous system
(PNS) and the central nervous system
(CNS) by the functional mechanisms and especially, the extent and speed.
Neuroscience
Neuroscience is the scientific study of the nervous system. Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics,...
and developmental biology
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
to describe the cellular and molecular mechanisms by which complex nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
s emerge during embryonic development
Morphogenesis
Morphogenesis , is the biological process that causes an organism to develop its shape...
and throughout life.
Some landmarks of embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
nic neural development include the birth and differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
of neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s from stem cell precursors, the migration
Cellular migration
Cellular migration is the movement of cells in the body to their proper position.-Purpose:During the Prenatal development, the basic structures for all organs in the body are created...
of immature neurons from their birthplaces in the embryo to their final positions, outgrowth of axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s from neurons and guidance
Axon guidance
Axon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach the correct targets...
of the motile growth cone
Growth cone
A growth cone is a dynamic, actin-supported extension of a developing axon seeking its synaptic target. Their existence was originally proposed by Spanish histologist Santiago Ramón y Cajal based upon stationary images he observed under the microscope...
through the embryo towards postsynaptic partners, the generation of synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
s between these axons and their postsynaptic partners, the neuron pruning
Synaptic pruning
In neuroscience, synaptic pruning, neuronal pruning or axon pruning refer to neurological regulatory processes, which facilitate a change in neural structure by reducing the overall number of neurons or connections, leaving more efficient synaptic configurations. Pruning is a neurological...
that occurs in adolescence
Adolescence
Adolescence is a transitional stage of physical and mental human development generally occurring between puberty and legal adulthood , but largely characterized as beginning and ending with the teenage stage...
, and finally the lifelong changes in synapses
Synaptic plasticity
In neuroscience, synaptic plasticity is the ability of the connection, or synapse, between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathways. Plastic change also results from the alteration of the number of receptors located on a synapse...
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
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
, migration
Cellular migration
Cellular migration is the movement of cells in the body to their proper position.-Purpose:During the Prenatal development, the basic structures for all organs in the body are created...
and axon guidance
Axon guidance
Axon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach the correct targets...
to their initial target areas. These processes are thought of as being independent of neural activity and sensory experience. Once axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s 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
Synaptic plasticity
In neuroscience, synaptic plasticity is the ability of the connection, or synapse, between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathways. Plastic change also results from the alteration of the number of receptors located on a synapse...
, which will be responsible for refinement of the nascent neural circuits.
Neurulation
- See embryogenesisEmbryogenesisEmbryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
for understanding the animal development up to this stage.
Neurulation is the formation of the neural tube
Neural tube
In the developing vertebrate, the neural tube is the embryo's precursor to the central nervous system, which comprises the brain and spinal cord...
from the ectoderm
Ectoderm
The "ectoderm" is one of the three primary germ cell layers in the very early embryo. The other two layers are the mesoderm and endoderm , with the ectoderm as the most exterior layer...
of the embryo. It follows gastrulation
Gastrulation
Gastrulation is a phase early in the embryonic development of most animals, during which the single-layered blastula is reorganized into a trilaminar structure known as the gastrula. These three germ layers are known as the ectoderm, mesoderm, and endoderm.Gastrulation takes place after cleavage...
in all vertebrates.
During gastrulation cells migrate to the interior of embryo, forming three germ layer
Germ layer
A germ layer, occasionally referred to as a germinal epithelium, is a group of cells, formed during animal embryogenesis. Germ layers are particularly pronounced in the vertebrates; however, all animals more complex than sponges produce two or three primary tissue layers...
s— the endoderm (the deepest layer), mesoderm and ectoderm (the surface layer)—from which all tissues and organs will arise. In a simplified way, it can be said that the ectoderm gives rise to skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
and nervous system, the endoderm to the guts
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
and the mesoderm to the rest of the organs.
After gastrulation the notochord
Notochord
The notochord is a flexible, rod-shaped body found in embryos of all chordates. It is composed of cells derived from the mesoderm and defines the primitive axis of the embryo. In some chordates, it persists throughout life as the main axial support of the body, while in most vertebrates it becomes...
—a flexible, rod-shaped body that runs along the back of the embryo—has been formed from the mesoderm. During the third week of gestation the notochord sends signals to the overlying ectoderm, inducing it to become neuroectoderm. This results in a strip of neuronal stem cells that runs along the back of the fetus. This strip is called the neural plate
Neural plate
In human embryology, formation of neural plate is the first step of neurulation. It is created by a flat thickening opposite to the primitive streak of the ectoderm.-Development:...
, and is the origin of the entire nervous system. The neural plate folds outwards to form the neural groove
Neural groove
The neural groove is a shallow median groove between the neural folds of an embryo. The neural folds are two longitudinal ridges that are caused by a folding up of the ectoderm in front of the primitive streak of the developing embryo...
. Beginning in the future neck region, the neural folds
Neural folds
In front of the primitive streak two longitudinal ridges, caused by a folding up of the ectoderm, make their appearance, one on either side of the middle line...
of this groove close to create the neural tube
Neural tube
In the developing vertebrate, the neural tube is the embryo's precursor to the central nervous system, which comprises the brain and spinal cord...
(this form of neurulation is called primary neuralation). The anterior (front) part of the neural tube is called the basal plate
Basal plate
Basal plate may refer to:* Basal plate , the region of the neural tube ventral to the sulcus limitans* Basal plate , between this plate and the uterine muscular fibres are the stratum spongiosum and the boundary layer...
; the posterior (rear) part is called the alar plate
Alar plate
The alar plate is a neural structure in the embryonic nervous system, part of the dorsal side of neural tube, that involves the communication of general somatic and general visceral sensory impulses. The caudal part later becomes sensory axon part of the spinal cord.-External links:* *...
. The hollow interior is called the neural canal. By the end of the fourth week of gestation, the open ends of the neural tube (the neuropores) close off.
Formation of the spinal cord
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.
Formation of the brain
Mesencephalon
The midbrain or mesencephalon is a portion of the central nervous system associated with vision, hearing, motor control, sleep/wake, arousal , and temperature regulation....
. Above the mesencephalon
Mesencephalon
The midbrain or mesencephalon is a portion of the central nervous system associated with vision, hearing, motor control, sleep/wake, arousal , and temperature regulation....
is the prosencephalon
Prosencephalon
In the anatomy of the brain of vertebrates, the prosencephalon is the rostral-most portion of the brain. The prosencephalon, the mesencephalon , and rhombencephalon are the three primary portions of the brain during early development of the central nervous system...
(future forebrain) and beneath it is the rhombencephalon
Rhombencephalon
The rhombencephalon is a developmental categorization of portions of the central nervous system in vertebrates.The rhombencephalon can be subdivided in a variable number of transversal swellings called rhombomeres...
(future hindbrain). The optical vesicle (which will eventually become the optic nerve, retina and iris) forms at the basal plate of the prosencephalon.
In the fifth week, the alar plate of the prosencephalon expands to form the cerebral hemispheres (the telencephalon
Telencephalon
The cerebrum or telencephalon, together with the diencephalon, constitutes the forebrain. The cerebrum is the most anterior region of the vertebrate central nervous system. Telencephalon refers to the embryonic structure, from which the mature cerebrum develops...
). The basal plate becomes the diencephalon
Diencephalon
The diencephalon is the region of the vertebrate neural tube which gives rise to posterior forebrain structures. In development, the forebrain develops from the prosencephalon, the most anterior vesicle of the neural tube which later forms both the diencephalon and the...
.
The diencephalon, mesencephalon and rhombencephalon constitute the brain stem
Brain stem
In vertebrate anatomy the brainstem is the posterior part of the brain, adjoining and structurally continuous with the spinal cord. The brain stem provides the main motor and sensory innervation to the face and neck via the cranial nerves...
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
Pons
The pons is a structure located on the brain stem, named after the Latin word for "bridge" or the 16th-century Italian anatomist and surgeon Costanzo Varolio . It is superior to the medulla oblongata, inferior to the midbrain, and ventral to the cerebellum. In humans and other bipeds this means it...
and the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
form in the upper part of the rhombencephalon, whilst the medulla oblongata forms in the lower part.
Human brain development
Neuronal migration
Neuronal migration
Cellular migration
Cellular migration is the movement of cells in the body to their proper position.-Purpose:During the Prenatal development, the basic structures for all organs in the body are created...
is the method by which neurons travel from their origin or birth place to their final position in the brain. There are several ways they can do this, e.g. by radial migration or tangential migration.
Radial migration
Neuronal precursor cells proliferate in the ventricular zone of the developing neocortexNeocortex
The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...
. The first postmitotic
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
cells to migrate form the preplate which are destined to become Cajal-Retzius cells and subplate
Subplate
The transient fetal subplate zone, together with the marginal zone and the cortical plate, represents the developmental anlage of the mammalian cerebral cortex...
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
Pia mater
Pia mater often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. The word finds its roots in Latin, meaning literally "tender mother." The other two meningeal membranes are the dura mater and the arachnoid mater....
. The soma
Soma (biology)
The soma , or perikaryon , or cyton, is the bulbous end of a neuron, containing the cell nucleus. The word "soma" comes from the Greek σῶμα, meaning "body"; the soma of a neuron is often called the "cell body"...
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
Centrosome
In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center of the animal cell as well as a regulator of cell-cycle progression. It was discovered by Edouard Van Beneden in 1883...
to guide the nucleus to its final destination. Radial fibres (also known as radial glia) can translocate to the cortical plate and differentiate either into astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s or neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s. Somal translocation can occur at any time during development.
Subsequent waves of neurons split the preplate by migrating along radial glia
Radial glia
Radial glial cells are a pivotal cell type in the developing central nervous system involved in key developmental processes, from patterning and neuronal migration to their recently discovered role as precursors during neurogenesis. They arise early in development from neuroepithelial cells...
l fibres to form the cortical plate. Each wave of migrating cells travel past their predecessors forming layers in an inside-out manner, meaning that the youngest neurons are the closest to the surface. It is estimated that glial guided migration represents 80-90% of migrating neurons.
Tangential migration
Most interneurons migrate tangentially through multiple modes of migration to reach their appropriate location in the cortex. An example of tangential migration is the movement of Cajal-Retzius cells from the cortical hem to the superfitial part of cortical neuroepithelium.Others
There is also a method of neuronal migration called multipolar migration. This is seen in multipolar cells, which are abundantly present in the cortical intermediate zone. They do not resemble the cells migrating by locomotion or somal translocation. Instead these multipolar cells express neuronal markers and extend multiple thin processes in various directions independently of the radial glial fibers.Neurotrophic factors
Neurotrophic factors are molecules which promote and regulate neuronal survival in the developing nervous system. They are distinguished from ubiquitous metaboliteMetabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
s necessary for cellular maintenance and growth by their specificity; each neurotrophic factor promotes the survival of only certain kinds of neurons during a particular stage of their development. In addition, it had been argued that neurotropihic factors are involved in many other aspects of neuronal development ranging from axonal guidance to regulation of neurotransmitter synthesis.
Neural development in the adult nervous system
Neurodevelopment in the adult nervous system includes mechanisms such as remyelinationRemyelination
Remyelination is a term for the re-generation of the nerve's myelin sheath, damaged in many diseases such as multiple sclerosis and the leukodystrophies. Remyelination is a subject of active medical research.-External links:**...
, generation of new neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s, glia, axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
s, myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
or synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
s. Neuroregeneration differs between the peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
(PNS) and the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS) by the functional mechanisms and especially, the extent and speed.
See also
- Time lapse seqeunces of radial migration (also known as glial guidance) and somal translocation.
- Axon guidanceAxon guidanceAxon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach the correct targets...
- Neural DarwinismNeural DarwinismNeural Darwinism, a large scale theory of brain function by Gerald Edelman, was initially published in 1978, in a book called The Mindful Brain...
- Pre- and perinatal psychologyPre- and perinatal psychologyPrenatal and perinatal psychology is an interdisciplinary study of the foundations of health in body, mind, emotions and in enduring response patterns to life...
- Neural developmentNeural developmentNeural development comprises the processes that generate, shape, and reshape the nervous system, from the earliest stages of embryogenesis to the final years of life. The study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms...