In the developing brain, MGE-derived interneuron precursors migrate tangentially long distances to reach the cortex in which they later establish connections with the principal cortical cells to control the activity of adult cortical circuits. Interneuron precursors exhibit complex morphologies and migratory properties, which are difficult to study in the heterogeneous and uncontrolled in vivo environment. Here, we describe two in vitro models in which the migration environment of interneuron precursors is significantly simplified and where their migration can be observed for one to 3 days. In one model, MGE-derived interneuron precursors are cultured and migrate on a flat synthetic substrate. In the other model, fluorescent MGE-derived interneuron precursors migrate on a monolayer of dissociated cortical cells. In both models, cell movements can be recorded by time-lapse microscopy for dynamic analyses.
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http://dx.doi.org/10.1007/978-1-4939-7701-7_12 | DOI Listing |
Adv Sci (Weinh)
January 2025
Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China.
Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder characterized by a range of clinical manifestations with no effective treatment strategy to date. Here, transplantation of GABAergic precursor cells from the medial ganglionic eminence (MGE) is demonstrated to significantly improve cognitive performance in Fmr1 knockout (KO) mice. Within the hippocampus of Fmr1-KO mice, MGE-derived cells from wild-type donor mice survive, migrate, differentiate into functionally mature interneurons, and form inhibitory synaptic connections with host pyramidal neurons.
View Article and Find Full Text PDFJ Neurochem
January 2025
Neurosciences and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.
The adult central nervous system (CNS) hosts several niches, in which the neural stem and precursor cells (NPCs) reside. The subventricular zone (SVZ) lines the lateral brain ventricles and the subgranular zone (SGZ) is located in the dentate gyrus of the hippocampus. SVZ and SGZ NPCs replace neurons and glia in the homeostatic as well as diseased or injured states.
View Article and Find Full Text PDFEpilepsia
December 2024
Department of Disease Model, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai, Aichi, Japan.
Objective: Loss-of-function mutations in the GIRDIN/CCDC88A gene cause developmental epileptic encephalopathy (DEE) in humans. However, its pathogenesis is largely unknown. Global knockout mice of the corresponding orthologous gene (gKOs) have a preweaning lethal phenotype with growth failure, preventing longitudinal analysis.
View Article and Find Full Text PDFMol Psychiatry
November 2024
Department of Molecular, Cell and Systems Biology, University of California Riverside, Riverside, CA, USA.
Dysregulation of development, migration, and function of interneurons, collectively termed interneuronopathies, have been proposed as a shared mechanism for autism spectrum disorders (ASDs) and childhood epilepsy. Neuropilin-2 (Nrp2), a candidate ASD gene, is a critical regulator of interneuron migration from the median ganglionic eminence (MGE) to the pallium, including the hippocampus. While clinical studies have identified Nrp2 polymorphisms in patients with ASD, whether selective dysregulation of Nrp2-dependent interneuron migration contributes to pathogenesis of ASD and enhances the risk for seizures has not been evaluated.
View Article and Find Full Text PDFNeonatal hypoxia (Hx) causes white matter (WM) injury, particularly in the cerebellum. We previously demonstrated that Hx-induced reduction of cerebellar Purkinje cell (PC) activity results in locomotor deficits. Yet, the mechanism of Hx-induced cerebellar WM injury and associated locomotor abnormalities remains undetermined.
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