Topic: microcephaly

We identified a clinical patient with a biallelic mutation in CETN3 exhibiting symptoms akin to microcephaly. This discovery prompted our investigation into the role of CETN3 in neurodevelopment. To delve deeper, we established a CETN3-KO H9 cell line and cultivated cerebral organoids using it. Mirroring the patient's phenotype, our cerebral organoids exhibited smaller sizes compared to the control group. Through immunofluorescence analysis, we observed that CETN3 deficiency interfered with neurodifferentiation and diminished the proliferation of neural stem cells. Additionally, our findings i

Proper interneuron migration and distribution are essential for optimal brain function. Disruptions of this process can impair the excitation/inhibition balance, leading to neurodevelopmental disorders. As such, ionizing radiation poses a particular risk to the developing brain, as it can lead to excessive fetal DNA damage and subsequent microcephaly. Although research on radiation-induced microcephaly has mainly focused on glutamatergic excitatory neurons, the impact on GABAergic interneurons is equally crucial. Understanding potential disruptions is essential for comprehensive insights into

Vaccinia-related kinase 1 (VRK1) is a predominantly nuclear serine/threonine kinase implicated in nucleus disassembly and reassembly, cell cycle, and transcription regulation. VRK1 mutations in humans have been linked to several neurodegenerative diseases, including spinal muscular atrophy associated with microcephaly and impaired cognitive and motor function. Thus, it has been identified as potentially involved in the maintenance and development of the nervous system. However, precise pathophysiological mechanisms and VRK1 involvement in cognitive and motor dysfunction progression have yet to

Microcephaly is a disease in which the head circumference and brain volume decrease. Patients with microcephaly show a range of cognitive deficits. One of the causes of microcephaly is mutations in the RTTN gene. RTTN mutations are responsible for syndromic malformations of cortical development. Here we have generated on-chip human brain organoids and 3D-hippocampal organoids to study the role of RTTN in the developing human brain.A RTTN homozygous pathogenic mutation was introduced in human embryonic stem cells using CRISPR/Cas9 genome editing. The developing control on-chip brain organoids e

Neurodevelopmental disorders (NDDs), such as intellectual disability (ID), can arise from genetic and environmental factors. PAK3, a gene crucial for brain development and synaptic plasticity, is involved in X-linked ID. Mutations in the PAK3 gene may also lead to autistic traits, epilepsy and other neurological symptoms. The most severe cases result from missense mutations in the kinase domain, rendering the protein stable but inactive.Our aim is to understand the specific effects of severe PAK3 variants on brain structure and function and assess the precise mechanism underlying severe PAK3-l