Development of the cerebral cortex
Neurons formed in the ventricular zone migrate to their final locations in one of the six layers of the cortex.
[2] The cortex is the outermost layer of the brain and consists primarily of gray matter, or neuronal cell bodies.
Interior areas of the brain consist of myelinated axons and appear as white matter.
Pioneer cells are also present in the subplate and work to create neuronal synapses within the plate.
[1] In early development, synaptic connections and circuits continue to proliferate at an exponential rate.
Instead these multipolar cells express neuronal markers and extend multiple thin processes in various directions independently of the radial glial fibers.
[1] Cajal-Retzius cells are also present in this zone and release reelin along the radial axis, a key signaling molecule in neuronal migration during corticogenesis.
Layer I is also characterized by expression of reelin, transcription factor T-box brain 1, and cortical migratory neuronal marker.
These layers are the last to form during corticogenesis and include pyramidal neurons, astrocytes, Stellates, and radial glial cells.
During the production of these layers, transcription factors TBR1 and OTX1 are expressed along with CTIP2, or corticoneuronal zinc finger protein.
While the majority of the process remains to be understood, some signals and pathways have been carefully unraveled in an effort to gain full knowledge of the mechanisms that control corticogenesis.
[10] Cajal-Retzius cells located in the marginal zone secrete reelin to start the cascade.
Reelin is secreted only by the Cajal-Retzius cells located in the marginal zone, and its receptors are confined to the cortical plate.
[1][6] Knocking out the Sonic hedgehog, or Shh, has been shown to severely affect corticogenesis in the genetically modified mice.
The ventral and dorsal sides of the cerebrum are affected as Shh expresses the transcription factors to Nkx2 which is important in patterning the cortex.
[11] In mice, bone morphogenetic protein 7 (Bmp-7), is an important regulator in corticogenesis, though it is not understood whether it promotes or inhibits neurogenesis.
For example, if Bmp-4 was absent from corticogenesis, very little would change in the cortex phenotype, due to the other Bmps helping accomplish the tasks of Bmp-4.
Cdh8 is known to be expressed in the intermediate and subventricular zone, though not in specific neurons in that area, and it is suggested to regulate fiber releasing.
[1] TSC, or tuberous sclerosis, is an autosomal dominant disorder that results in formation of tumors along neuroectodermally-derived tissue.
When inactivation of TSC1 is present during corticogenesis, malformations of cortical tubers, or abnormal benign tissue growth, along with white matter nodes would form in mice.
[17] [18] Recapitulation of corticogenesis in both human and mouse embryos has been accomplished with a three dimensional culture using embryonic stem cells (ESC).
By carefully using embryo body intermediates and cultured in a serum free environment cortical progenitors form in a space and time related pattern similar to in vivo corticogenesis.
Using immunocytochemical analysis on mouse neural stem cells derived from ESCs, after 6 days there was evidence of neuronal differentiation.
