Radial unit hypothesis
{{Short description|Conceptual theory of cerebral cortex development}}
{{technical|date=February 2017}}
The Radial Unit Hypothesis (RUH) is a conceptual theory of cerebral cortex development, first described by Pasko Rakic. It states that the cerebral cortex develops during embryogenesis as an array of interacting cortical columns, or 'radial units', each of which originates from a transient stem cell layer called the ventricular zone, which contains neural stem cells known as radial glial cells.{{cite journal|last1=Rakic|first1=P|title=Specification of cerebral cortical areas.|journal=Science|date=8 July 1988|volume=241|issue=4862|pages=170–6|pmid=3291116|doi=10.1126/science.3291116}}{{cite journal|last1=Rakic|first1=P|title=A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution.|journal=Trends in Neurosciences|date=September 1995|volume=18|issue=9|pages=383–8|pmid=7482803|doi=10.1016/0166-2236(95)93934-p|s2cid=11913076|doi-access=free}}
Cortical evolution
The reiterative nature of the cerebral cortex, in the sense that it is a vast array of repeating functional circuits, led to the idea that cortical evolution is governed by mechanisms regulating the addition of cortical columns, enabling additional functional areas to become specialized and incorporated into the brain. The addition of new radial units is thought to depend on control of the cell cycle (proliferation) of cortical stem cells lining the ventricular system in the ventricular zone and subventricular zone.{{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}}
Protomap
Intimately related to the RUH is the 'protomap' hypothesis, which states that the primordial identity of each functional area of the cerebral cortex is encoded within the cortical stem cells prior to the formation of the cortical layers. Within each developing radial unit, the process of neurogenesis gives rise to post-mitotic (non-dividing) cortical neurons, which begin the process of radial neuronal migration from the ventricular zone and adjacent subventricular zone to form the cortical plate in the classic 'inside-out' manner beginning with the deep cortical layers.{{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|s2cid=41001390}}{{cite journal|last1=Rakic|first1=P|title=Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition.|journal=Science|date=1 February 1974|volume=183|issue=4123|pages=425–7|pmid=4203022|doi=10.1126/science.183.4123.425|s2cid=10881759}} Once their final destination is achieved, cortical neurons begin to form circuits with other cortical and subcortical neurons, often taking on a columnar shape following the radial migration route.{{cite journal|last1=Yuste|first1=R|last2=Peinado|first2=A|last3=Katz|first3=LC|title=Neuronal domains in developing neocortex.|journal=Science|date=31 July 1992|volume=257|issue=5070|pages=665–9|pmid=1496379|doi=10.1126/science.1496379}} Some localized lateral dispersion takes place during cortical column development in the mouse, but the degree of dispersion is molecularly regulated and indeed could vary across species.{{cite journal|last1=Torii|first1=M|last2=Hashimoto-Torii|first2=K|last3=Levitt|first3=P|last4=Rakic|first4=P|title=Integration of neuronal clones in the radial cortical columns by EphA and ephrin-A signalling.|journal=Nature|date=24 September 2009|volume=461|issue=7263|pages=524–8|pmid=19759535|doi=10.1038/nature08362|pmc=2874978}}
Principles of development
Together, the RUH and protomap hypothesis represent two core principles of early cerebral cortex development. After neurons arrive in the cortical plate, other processes—especially activity-dependent processes—govern the maturation of cortical circuitry.{{cite journal|last1=Ackman|first1=JB|last2=Burbridge|first2=TJ|last3=Crair|first3=MC|title=Retinal waves coordinate patterned activity throughout the developing visual system.|journal=Nature|date=11 October 2012|volume=490|issue=7419|pages=219–25|pmid=23060192|doi=10.1038/nature11529|pmc=3962269}}