In vertebrates, a neuroblast or primitive nerve cell is a postmitotic cell that does not divide further, and which will develop into a

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa ...

after a

migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...

phase. In invertebrates such as ''Drosophila,'' neuroblasts are neural progenitor cells which divide asymmetrically to produce a neuroblast, and a daughter cell of varying potency depending on the type of neuroblast. Vertebrate neuroblasts differentiate from

radial glial cell Radial glial cells, or radial glial progenitor cells (RGPs), are bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including astrocytes and ...

s and are committed to becoming neurons.

Neural stem cell Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor ste ...

s, which only divide symmetrically to produce more neural stem cells, transition gradually into

s. Radial glial cells, also called radial glial progenitor cells, divide asymmetrically to produce a neuroblast and another radial glial cell that will re-enter the cell cycle. This

mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintai ...

occurs in the germinal

neuroepithelium Neuroepithelial cells, or neuroectodermal cells, form the wall of the closed neural tube in early embryonic development. The neuroepithelial cells span the thickness of the tube's wall, connecting with the pial surface and with the ventricular or ...

(or germinal zone), when a radial glial cell divides to produce the neuroblast. The neuroblast detaches from the epithelium and migrates while the radial glial progenitor cell produced stays in the lumenal epithelium. The migrating cell will not divide further and this is called the neuron's birthday. Cells with the earliest birthdays will only migrate a short distance. Those cells with later birthdays will migrate further to the more outer regions of the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...

. The positions that the migrated cells occupy will determine their neuronal differentiation.

Formation

Neuroblasts are formed by the asymmetric division of radial glial cells. They start to migrate as soon as they are born.

Neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). It occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NEC ...

can only take place when neural stem cells have transitioned into radial glial cells.

Differentiation

Neuroblasts are mainly present as precursors of neurons during embryonic development; however, they also constitute one of the cell types involved in

adult neurogenesis Adult neurogenesis is the process in which neurons are generated from neural stem cells in the adult. This process differs from prenatal neurogenesis. In most mammals, new neurons are born throughout adulthood in two regions of the brain: * Th ...

. Adult neurogenesis is characterized by neural stem cell differentiation and integration in the mature adult mammalian brain. This process occurs in the

dentate gyrus The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute t ...

of the hippocampus and in the

subventricular zone The subventricular zone (SVZ) is a region situated on the outside wall of each lateral ventricle of the vertebrate brain. It is present in both the embryonic and adult brain. In embryonic life, the SVZ refers to a secondary proliferative zone ...

s of the adult mammalian brain. Neuroblasts are formed when a

neural stem cell Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor ste ...

, which can differentiate into any type of mature neural cell (i.e. neurons,

oligodendrocyte Oligodendrocytes (), or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of jawed vertebrates, equivalent to the function performed by Schwann cells in the ...

astrocyte Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of e ...

s, etc.), divides and becomes a transit amplifying cell. Transit amplifying cells are slightly more differentiated than neural stem cells and can divide asymmetrically to produce postmitotic neuroblasts and glioblasts, as well as other transit amplifying cells. A neuroblast, a daughter cell of a transit amplifying cell, is initially a neural stem cell that has reached the "point of no return." A neuroblast has differentiated such that it will mature into a neuron and not any other neural cell type. Neuroblasts are being studied extensively as they have the potential to be used therapeutically to combat cell loss due to injury or disease in the brain, although their potential effectiveness is debated.

Migration

In the

embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

neuroblasts form the middle mantle layer of the

neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural fold become elevated, ...

wall which goes on to form the

grey matter Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil ( dendrites and unmyelinated axons), glial cells ( astrocytes and oligodendrocytes), synapses, and capillaries. Grey matter is ...

of the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the sp ...

. The outer layer to the mantle layer is the marginal layer and this contains the myelinated axons from the neuroblasts forming the

white matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribu ...

of the spinal cord. The inner layer is the ependymal layer that will form the lining of the ventricles and

central canal The central canal (also known as spinal foramen or ependymal canal) is the cerebrospinal fluid-filled space that runs through the spinal cord. The central canal lies below and is connected to the ventricular system of the brain, from which it ...

of the spinal cord. In humans, neuroblasts produced by stem cells in the adult

migrate into damaged areas after brain injuries. However, they are restricted to the subtype of small interneuron-like cells, and it is unlikely that they contribute to functional recovery of

striatal The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamate ...

circuits.

Clinical significance

There are several disorders known as

neuronal migration disorder Neuronal migration disorder (NMD) refers to a heterogenous group of disorders that, it is supposed, share the same etiopathological mechanism: a variable degree of disruption in the migration of neuroblasts during neurogenesis. The neuronal migr ...

s that can cause serious problems. These arise from a disruption in the pattern of migration of the neuroblasts on their way to their target destinations. The disorders include,

lissencephaly Lissencephaly (, meaning "smooth brain") is a set of rare brain disorders whereby the whole or parts of the surface of the brain appear smooth. It is caused by defective neuronal migration during the 12th to 24th weeks of gestation resulting in ...

microlissencephaly Microlissencephaly (MLIS) is a rare congenital brain disorder that combines severe microcephaly (small head) with lissencephaly (smooth brain surface due to absent sulci and gyri). Microlissencephaly is a heterogeneous disorder, i.e. it has many d ...

, pachygyria, and several types of gray matter heterotopia.

Neuroblast development in Drosophila

In the fruit fly

model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...

,'' a neuroblast is a neural progenitor cell which divides asymmetrically to produce a neuroblast and either a neuron, a

ganglion mother cell Ganglion mother cells (GMCs) are cells involved in neurogenesis, in non-mammals, that divide only once to give rise to two neurons, or one neuron and one glial cell or two glial cells, and are present only in the central nervous system. They are al ...

(GMC), or an intermediate neural progenitor, depending on the type of neuroblast. During

embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

, embryonic neuroblasts delaminate from either the procephalic neuroectoderm (for brain neuroblasts), or the

ventral nerve cord The ventral nerve cord is a major structure of the invertebrate central nervous system. It is the functional equivalent of the vertebrate spinal cord. The ventral nerve cord coordinates neural signaling from the brain to the body and vice versa, i ...

neuroectoderm (for abdominal neuroblasts). During larval development, optic lobe neuroblasts are generated from a neuroectoderm called the Outer Proliferation Center. There are more than 800 optic lobe neuroblasts, 105 central brain neuroblasts, and 30 abdominal neuroblasts per hemisegment (a bilateral half of a segment). Neuroblasts undergo three known division types. Type 0 neuroblasts divide to give rise to a neuroblast, and a daughter cell which directly differentiates into a single neuron or glia. Type I neuroblasts give rise to a neuroblast and a

(GMC), which undergoes a terminal division to generate a pair of sibling neurons. This is the most common form of cell division, and is observed in abdominal, optic lobe, and central brain neuroblasts. Type II neuroblasts give rise to a neuroblast and a transit amplifying Intermediate Neural Progenitor (INP). INPs divide in a manner similar to type I neuroblasts, producing an INP and a ganglion mother cell. While only 8 type II neuroblasts exist in the central brain, their lineages are both much larger and more complex than type I neuroblasts. The switch from pluripotent neuroblast to differentiated cell fate is facilitated by the proteins Prospero, Numb, and Miranda. Prospero is a transcription factor that triggers differentiation. It is expressed in neuroblasts, but is kept out of the nucleus by Miranda, which tethers it to the cell basal cortex. This also results in asymmetric division, where Prospero localizes in only one out of the two daughter cells. After division, Prospero enters the nucleus, and the cell it is present in becomes the GMC. Neuroblasts are capable of giving rise to the vast neural diversity present in the fly brain using a combination of spatial and temporal restriction of gene expression that give progeny born from each neuroblast a unique identity depending both their parent neuroblast and their birth date. This is partly based on the position of the neuroblast along the Anterior/Posterior and Dorsal/Ventral axes, and partly on a temporal sequence of transcription factors that are expressed in a specific order as neuroblasts undergo sequential divisions.

References