Related Experiment Video

Updated: Feb 8, 2026

Robust and Highly Reproducible Generation of Cortical Brain Organoids for Modelling Brain Neuronal Senescence In Vitro
05:40

Robust and Highly Reproducible Generation of Cortical Brain Organoids for Modelling Brain Neuronal Senescence In Vitro

Published on: May 5, 2022

4.5K

Brain Somatic Mutations in MTOR Disrupt Neuronal Ciliogenesis, Leading to Focal Cortical Dyslamination

Sang Min Park1, Jae Seok Lim2, Suresh Ramakrishina3

  • 1Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.

Neuron
|June 26, 2018
PubMed

Insights

Brain somatic mutations in MTOR disrupt neuronal ciliogenesis, leading to cortical dyslamination in focal malformations of cortical development (FMCDs). This impacts Wnt signaling, causing pediatric intractable epilepsies.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Focal malformations of cortical development (FMCDs), including focal cortical dysplasia (FCD) and hemimegalencephaly (HME), are key causes of pediatric intractable epilepsies.
  • Cortical dyslamination is a hallmark of FMCDs.
  • Brain somatic mutations in MTOR are increasingly recognized as a genetic driver of FMCDs, but the underlying molecular mechanisms are unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism linking MTOR mutations to cortical dyslamination in FMCDs.
  • To investigate the role of neuronal ciliogenesis in the pathogenesis of FMCDs.

Main Methods:

  • Utilized patient-derived tissues, genome-edited cellular models, and mouse models harboring brain somatic MTOR mutations.
  • Examined neuronal ciliogenesis, autophagy, OFD1 localization, and Wnt signaling pathways.

Main Results:

  • Disruption of neuronal ciliogenesis by MTOR mutations was identified as a direct cause of cortical dyslamination in FMCDs.
  • Abnormal OFD1 accumulation at centriolar satellites, driven by perturbed autophagy, impaired ciliogenesis.
  • Impaired neuronal ciliogenesis compromised Wnt signaling, essential for neuronal polarization, thereby contributing to cortical dyslamination.

Conclusions:

  • MTOR mutations disrupt neuronal ciliogenesis via OFD1 accumulation and perturbed autophagy, leading to cortical dyslamination in FMCDs.
  • This mechanism highlights the critical role of ciliogenesis and Wnt signaling in the pathogenesis of MTOR-related cortical developmental disorders and pediatric epilepsies.
Keywords:
MTORbrain somatic mutationfocal malformations of cortical developmentprimary cilia

More Related Videos

Modeling Stroke in Mice: Focal Cortical Lesions by Photothrombosis06:07

Modeling Stroke in Mice: Focal Cortical Lesions by Photothrombosis

Published on: May 6, 2021

7.7K
Preparation of Dissociated Mouse Cortical Neuron Cultures18:02

Preparation of Dissociated Mouse Cortical Neuron Cultures

Published on: December 19, 2007

45.2K

Related Concept Videos

Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
14.9K
Mutations01:39

Mutations

Overview
94.6K
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.6K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
39.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.6K