1. Figure 2 Pathophysiological mechanisms in
malformations of cortical development caused by somatic mutations
Figure 2 | Pathophysiological mechanisms in malformations of cortical development caused by somatic mutations. The figure depicts the effects of a somatic mutation in a gene that regulates mechanistic target of rapamycin (mTOR) function (PI3K, AKT3, DEPDC5) that occurs in one of the neuroglial progenitor cells (light red) within the ventricular zone of the embryonic brain. When the progenitor cells carrying the mutation (red) undergo mitosis, the number of cells containing the mutant alleles increases. Cells migrate to the cortical plate but cannot form appropriate laminae owing to impaired migration, loss of laminar cues, or failed differentiation as a consequence of the gene mutation (cell-autonomous effects), resulting in a malformation of cortical development (MCD) — for example, focal cortical dysplasia (FCD) or hemimegalencephaly (HME). Because the mutation occurs by a somatic mechanism, the MCD contains a mixture of aberrant cell types (red) that contain a mutation and normal cells (light red) with a regular genotype. The cerebral cortex surrounding the MCD is histologically normal (light red neurons).
Crino, P. B. (2016) The mTOR signalling cascade: paving new roads to cure neurological disease
Nat. Rev. Neurol. doi: /nrneurol