Ventricular zone
{{short description|Transient embryonic layer of tissue containing neural stem cells}}
File:WikiVZSVZ.jpg of Sox2 and Tbr2 gene expression in the embryonic mouse forebrain at embryonic day 13.5. The dorsal telencephalon becomes the cerebral cortex, and contains the Tbr2-labeled cells. CP, cortical plate; LV, lateral ventricle; MGE, medial ganglionic eminence]]
In vertebrates, the ventricular zone (VZ) is a transient embryonic layer of tissue containing neural stem cells, principally radial glial cells, of the central nervous system (CNS).{{cite journal|last1=Rakic|first1=P|title=Evolution of the neocortex: a perspective from developmental biology.|journal=Nature Reviews. Neuroscience|date=October 2009|volume=10|issue=10|pages=724–35|pmid=19763105|doi=10.1038/nrn2719|pmc=2913577}}{{cite journal|last1=Noctor|first1=SC|last2=Flint|first2=AC|last3=Weissman|first3=TA|last4=Dammerman|first4=RS|last5=Kriegstein|first5=AR|title=Neurons derived from radial glial cells establish radial units in neocortex.|journal=Nature|date=8 February 2001|volume=409|issue=6821|pages=714–20|pmid=11217860|doi=10.1038/35055553}} The VZ is so named because it lines the ventricular system, which contains cerebrospinal fluid (CSF). The embryonic ventricular system contains growth factors and other nutrients needed for the proper function of neural stem cells.{{cite journal|last1=Lehtinen|first1=MK|last2=Zappaterra|first2=MW|last3=Chen|first3=X|last4=Yang|first4=YJ|last5=Hill|first5=AD|last6=Lun|first6=M|last7=Maynard|first7=T|last8=Gonzalez|first8=D|last9=Kim|first9=S|last10=Ye|first10=P|last11=D'Ercole|first11=AJ|last12=Wong|first12=ET|last13=LaMantia|first13=AS|last14=Walsh|first14=CA|title=The cerebrospinal fluid provides a proliferative niche for neural progenitor cells.|journal=Neuron|date=10 March 2011|volume=69|issue=5|pages=893–905|pmid=21382550|doi=10.1016/j.neuron.2011.01.023|pmc=3085909}} Neurogenesis, or the generation of neurons, occurs in the VZ during embryonic and fetal development as a function of the Notch pathway,{{cite journal|last1=Kageyama|first1=R|last2=Ohtsuka|first2=T|last3=Shimojo|first3=H|last4=Imayoshi|first4=I|title=Dynamic Notch signaling in neural progenitor cells and a revised view of lateral inhibition.|journal=Nature Neuroscience|date=November 2008|volume=11|issue=11|pages=1247–51|pmid=18956012|doi=10.1038/nn.2208}}{{cite journal|last1=Rash|first1=BG|last2=Lim|first2=HD|last3=Breunig|first3=JJ|last4=Vaccarino|first4=FM|title=FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis.|journal=The Journal of Neuroscience|date=26 October 2011|volume=31|issue=43|pages=15604–17|pmid=22031906|doi=10.1523/jneurosci.4439-11.2011|pmc=3235689}} and the newborn neurons must migrate substantial distances to their final destination in the developing brain or spinal cord where they will establish neural circuits.{{cite journal|last1=Rakic|first1=P|title=Neuron-glia relationship during granule cell migration in developing cerebellar cortex. A Golgi and electronmicroscopic study in Macacus Rhesus.|journal=The Journal of Comparative Neurology|date=March 1971|volume=141|issue=3|pages=283–312|pmid=4101340|doi=10.1002/cne.901410303}}{{cite journal|last1=Rakic|first1=P|title=Mode of cell migration to the superficial layers of fetal monkey neocortex.|journal=The Journal of Comparative Neurology|date=May 1972|volume=145|issue=1|pages=61–83|pmid=4624784|doi=10.1002/cne.901450105}} A secondary proliferative zone, the subventricular zone (SVZ), lies adjacent to the VZ. In the embryonic cerebral cortex, the SVZ contains intermediate neuronal progenitors that continue to divide into post-mitotic neurons.{{cite journal|last1=Noctor|first1=SC|last2=Martínez-Cerdeño|first2=V|last3=Ivic|first3=L|last4=Kriegstein|first4=AR|title=Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases.|journal=Nature Neuroscience|date=February 2004|volume=7|issue=2|pages=136–44|pmid=14703572|doi=10.1038/nn1172}}{{cite journal|last1=Hevner|first1=RF|last2=Haydar|first2=TF|title=The (not necessarily) convoluted role of basal radial glia in cortical neurogenesis.|journal=Cerebral Cortex|date=February 2012|volume=22|issue=2|pages=465–8|pmid=22116731|doi=10.1093/cercor/bhr336|pmc=3256413}} Through the process of neurogenesis, the parent neural stem cell pool is depleted and the VZ disappears.{{cite journal|last1=Dehay|first1=C|last2=Kennedy|first2=H|title=Cell-cycle control and cortical development.|journal=Nature Reviews. Neuroscience|date=June 2007|volume=8|issue=6|pages=438–50|pmid=17514197|doi=10.1038/nrn2097}} The balance between the rates of stem cell proliferation and neurogenesis changes during development,{{cite journal|last1=Takahashi|first1=T|last2=Nowakowski|first2=RS|last3=Caviness VS|first3=Jr|title=The leaving or Q fraction of the murine cerebral proliferative epithelium: a general model of neocortical neuronogenesis.|journal=The Journal of Neuroscience|date=1 October 1996|volume=16|issue=19|pages=6183–96|doi=10.1523/JNEUROSCI.16-19-06183.1996|pmid=8815900|pmc=6579174}} and species from mouse to human show large differences in the number of cell cycles, cell cycle length, and other parameters, which is thought to give rise to the large diversity in brain size and structure.
Epigenetic DNA modifications appear to have a central role in regulating gene expression during differentiation of neural stem cells. One type of epigenetic modification occurring in the VZ is the formation of DNA 5-Methylcytosine from cytosine by DNA methyltransferases.Wang Z, Tang B, He Y, Jin P. DNA methylation dynamics in neurogenesis. Epigenomics. 2016 Mar;8(3):401-14. {{doi|10.2217/epi.15.119}}. Epub 2016 Mar 7. Review. {{PMID|26950681}} Another important type of epigenetic modification is the demethylation of 5mC, catalyzed in several steps by TET enzymes and enzymes of the base excision repair pathway.