File:Molecular regulation of cerebral cortex folding by Trnp1.jpg

English: diagram depicting how gene Trnp1 controls folding of the cortical sheet in the mammalian brain. caption: (a) In the developing mouse cerebral cortex, early progenitors (E12) express high levels of Trnp1 (dark red), leading to their self-renewal and tangential expansion of the neuroepithelium. At mid-stages (E14) Trnp1 expression is downregulated (pale red) in a salt-and-pepper fashion, leading to a mixed tangential and radial expansion. Focal knock-down of Trnp1 (i.e. by shRNA) causes a rapid radial expansion of this region (right). At late stages (E16) Trnp1 is downregulated, causing radial growth in detriment of tangential growth. (b) The downregulation of Trnp1 in an entire region (not salt-and-pepper), either by shRNA in mouse or by the natural expression pattern in humans, increases the delamination of aRG (red) to generate abundant bRGCs (including bpRG) and IPCs (green), which locally increase the number of neurons generated (blue) and the divergence of radial fibers (black lines), hence expanding cortical surface area. Because this occurs only locally, a cortical fold is formed in between regions with relatively higher Trnp1 expression and hence less radial/basal expansion. Importantly, the outer cortical surface folds (top), but not the ventricular surface (bottom). Overexpression of Cdk4/CyclinD1 (green background) in basal progenitors causes their overproliferation and increased cortical folding in ferrets, but not in mice.