FIGURE 2.

Defective ciliogenesis due to brain somatic mutations in MTOR accounts for cortical dyslamination in FMCDs. (A) Representative brain MRIs of patients with FMCDs, including hemimegalencephaly (HME) and focal cortical dysplasia (FCD) type II. Arrows indicate the affected region of the brain. Adapted from Park et al. (2018), with permission. (B) Immunostaining for Arl13b, a marker for primary cilia, and NeuN, a marker for neurons, with DAPI co-staining in brain tissue from FMCD patients. While primary cilium normally forms at each neuron in brain tissue from non-FMCD, FMCD patients with brain somatic mutations in MTOR exhibit defective neuronal ciliogenesis. Scale bars, 30 μm. Adapted from Park et al. (2018), with permission. (C) Autophagic degradation of the centriolar satellite pool of OFD1 induces primary ciliogenesis. However, brain somatic activating mutation in MTOR, which blocks autophagy, disrupts ciliogenesis in brain tissues with FMCDs. (D) Cortical dyslamination with ciliary defective dysmorphic neurons in the cerebral cortex of a FMCD patient. Somatic activating mutations in MTOR, causative for FMCDs, disrupt neuronal ciliogenesis through blockage of autophagy, resulting in cortical dyslamination.