Editing Neuroblast

{{short description|Non-dividing precursor cell to a neuron}}
In vertebrates, a '''neuroblast''' or '''primitive nerve cell'''<ref name="Sadler">{{cite book|last1=Sadler|first1=T.|title=Langman's medical embryology.|url=https://archive.org/details/langmansmedicale00sadl_655|url-access=limited|date=2010|publisher=Lippincott William & Wilkins|location=Philadelphia|isbn=978-07817-9069-7|pages=[https://archive.org/details/langmansmedicale00sadl_655/page/n307 296]–297|edition=11th}}</ref> is a [[G0 phase|postmitotic cell]] that does not divide further,<ref name="Williams">{{cite web |last1=Williams |first1=S. Mark |last7=Purves |first7=Dale |title=The Initial Formation of the Nervous System: Gastrulation and Neurulation |url=https://www.ncbi.nlm.nih.gov/books/NBK10993/ |website=Neuroscience. 2nd edition |access-date=5 January 2019 |language=en |date=2001}}</ref> and which will develop into a [[neuron]] after a [[Cell migration|migration]] phase.<ref name="Purves2012">{{cite book |last1=Purves |first1=Dale |title=Neuroscience |date=2012 |publisher=Sinauer Associates |isbn=9780878936953 |pages=490 |edition=5th}}</ref> 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 [[Cellular differentiation|differentiate]] from [[radial glial cell]]s and are committed to becoming neurons.<ref name="urlwberesford.hsc.wvu.edu">{{cite web |url=http://wberesford.hsc.wvu.edu/histolch10.htm |title=wberesford.hsc.wvu.edu |access-date=2010-04-08}}</ref> [[Neural stem cell]]s, which only divide symmetrically to produce more neural stem cells, transition gradually into [[radial glial cell]]s.<ref name="Johnson">{{cite journal |last1=Johnson |first1=CA |last2=Wright |first2=CE |last3=Ghashghaei |first3=HT |title=Regulation of cytokinesis during corticogenesis: focus on the midbody. |journal=FEBS Letters |date=December 2017 |volume=591 |issue=24 |pages=4009–4026 |doi=10.1002/1873-3468.12676 |pmid=28493553|doi-access=free }}</ref> Radial glial cells, also called radial glial progenitor cells, divide [[Asymmetric cell division|asymmetrically]] to produce a neuroblast and another radial glial cell that will re-enter the cell cycle.<ref name="Johnson"/><ref name="Purves2012"/>

This [[mitosis]] occurs in the germinal [[neuroepithelial cell|neuroepithelium]] (or germinal zone), when a radial glial cell divides to produce the neuroblast. The neuroblast detaches from the epithelium and [[cellular migration|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 positions that the migrated cells occupy will determine their neuronal differentiation.<ref name="Gilbert">{{cite book |last1=Gilbert |first1=Scott |title=Developmental biology |url=https://archive.org/details/developmentalbio00gilb_292 |url-access=limited |date=2006 |publisher=Sinauer Associates Publishers |isbn=9780878932504 |pages=[https://archive.org/details/developmentalbio00gilb_292/page/n405 386]–387 |edition=8th}}</ref>

==Formation==
Neuroblasts are formed by the [[asymmetric cell division|asymmetric division]] of radial glial cells. They start to migrate as soon as they are born. [[Neurogenesis]] can only take place when neural stem cells have transitioned into radial glial cells.<ref name="Johnson"/>

===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 characterized by neural stem cell differentiation and integration in the mature adult mammalian brain. This process occurs in the [[dentate gyrus]] of the hippocampus and in the [[subventricular zone]]s of the adult mammalian brain. Neuroblasts are formed when a [[neural stem cell]], which can differentiate into any type of mature neural cell (i.e. neurons, [[oligodendrocyte]]s, [[astrocyte]]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.<ref>{{cite book|last=Purves|first=D|title=Neuroscience |year=2007|publisher=W. H. Freeman|location=New York|isbn=978-0-87893-697-7|edition=4th|display-authors=etal}}{{page needed|date=April 2018}}</ref> 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]] neuroblasts form the middle '''mantle layer''' of the [[neural tube]] wall which goes on to form the [[grey matter]] of the [[spinal cord]]. The outer layer to the mantle layer is the '''marginal layer''' and this contains the myelinated axons from the neuroblasts forming the [[white matter]] of the spinal cord.<ref name="Sadler"/> The inner layer is the [[ependyma|ependymal layer]] that will form the lining of the [[ventricular system|ventricles]] and [[central canal]] of the spinal cord.<ref name="Tortora">{{cite book |last1=Tortora |first1=G |last2=Derrickson |first2=B |title=Principles of anatomy & physiology. |date=2011 |publisher=Wiley |isbn=9780470646083 |page=571 |edition=13th.}}</ref>

In humans, neuroblasts produced by stem cells in the adult [[subventricular zone]] [[cell migration|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 [[Striatum|striatal]] circuits.<ref name="Liu">{{cite journal | last1=Liu | first1=F | title=Brain Injury Does Not Alter the Intrinsic Differentiation Potential of Adult Neuroblasts | journal=The Journal of Neuroscience | volume=29 | issue=16 | pages=5075–5087 |date=April 2009 | doi=10.1523/JNEUROSCI.0201-09.2009 | pmid=19386903 | last2=You | first2=Y | last3=Li | first3=X | last4=Ma | first4=T | last5=Nie | first5=Y | last6=Wei | first6=B | last7=Li | first7=T | last8=Lin | first8=H | last9=Yang | first9=Z | pmc=6665479 | doi-access=free }}</ref>

==Clinical significance==
There are several disorders known as [[neuronal migration disorder]]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]], [[microlissencephaly]], [[pachygyria]], and several types of [[gray matter heterotopia]].

== Neuroblast development in ''Drosophila'' ==
In the fruit fly [[model organism]] ''[[Drosophila melanogaster]],'' a neuroblast is a neural progenitor cell which divides asymmetrically to produce a neuroblast and either a neuron, a [[ganglion mother cell]] (GMC), or an intermediate neural progenitor, depending on the type of neuroblast.<ref name="Gaillaud">{{cite book |last1=Gallaud |first1=E |last2=Pham |first2=T |last3=Cabernard |first3=C |title=Asymmetric Cell Division in Development, Differentiation and Cancer |chapter=Drosophila melanogaster Neuroblasts: A Model for Asymmetric Stem Cell Divisions |series=Results and Problems in Cell Differentiation |date=2017 |volume=61 |pages=183–210 |doi=10.1007/978-3-319-53150-2_8 |pmid=28409305|isbn=978-3-319-53149-6 }}</ref><ref name=":0">{{Cite journal|last=Doe|first=Chris Q.|date=2017-10-06|title=Temporal Patterning in the Drosophila CNS|journal=Annual Review of Cell and Developmental Biology|language=en|volume=33|issue=1|pages=219–240|doi=10.1146/annurev-cellbio-111315-125210|pmid=28992439|issn=1081-0706|doi-access=free}}</ref> During [[Embryonic development|embryogenesis]], embryonic neuroblasts delaminate from either the procephalic neuroectoderm (for brain neuroblasts), or the [[ventral nerve cord]] neuroectoderm (for abdominal neuroblasts). During larval development, [[Optic lobe (arthropods)|optic lobe]] neuroblasts are generated from a neuroectoderm called the Outer Proliferation Center.<ref>{{Cite journal|last1=Courgeon|first1=Maximilien|last2=Desplan|first2=Claude|date=2019-06-01|title=Coordination of neural patterning in the Drosophila visual system|url= |journal=Current Opinion in Neurobiology|series=Neuronal Identity|language=en|volume=56|pages=153–159|doi=10.1016/j.conb.2019.01.024|pmid=30849690|issn=0959-4388|pmc=6551251}}</ref> There are more than 800 optic lobe neuroblasts, 105 central brain neuroblasts, and 30 abdominal neuroblasts per hemisegment (a bilateral half of a segment).<ref name=":0" />

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 [[ganglion mother cell]] (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.<ref name=":0" /> The switch from pluripotent neuroblast to differentiated cell fate is facilitated by the proteins Prospero, [[NUMB (gene)|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.<ref>{{Cite journal|last1=Sen|first1=Sonia Q|last2=Chanchani|first2=Sachin|last3=Southall|first3=Tony D|last4=Doe|first4=Chris Q|date=2019-01-29|editor-last=Mandel|editor-first=Gail|editor2-last=Struhl|editor2-first=Kevin|editor3-last=Desplan|editor3-first=Claude|editor4-last=Eisen|editor4-first=Michael B|title=Neuroblast-specific open chromatin allows the temporal transcription factor, Hunchback, to bind neuroblast-specific loci|journal=eLife|volume=8|pages=e44036|doi=10.7554/eLife.44036|pmid=30694180|pmc=6377230|issn=2050-084X|doi-access=free}}</ref> 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.<ref>{{cite journal |last1=Kohwi |first1=M |last2=Hiebert |first2=LS |last3=Doe |first3=CQ |title=The pipsqueak-domain proteins Distal antenna and Distal antenna-related restrict Hunchback neuroblast expression and early-born neuronal identity. |journal=Development |date=May 2011 |volume=138 |issue=9 |pages=1727–35 |doi=10.1242/dev.061499 |pmid=21429984 |pmc=3074449 }}</ref>

== See also ==
* [[Neuroblastoma]]
* [[Posterior column]]
* [[List of human cell types derived from the germ layers]]

== References ==
{{Reflist}}

{{Development of nervous system}}

[[Category:Embryology of nervous system]]
[[Category:Cell biology]]