GABAergic neurons are an essential cellular component of neural circuits. Their abundance and diversity have enlarged significantly in the human brain, contributing to the expanded cognitive capacity of humans. However, the developmental mechanism of the extended production of GABAergic neurons in the human brain remains elusive. Here, we use single-cell transcriptomics, bioinformatics, and histological analyses to uncover microglial regulation of the sustained proliferation of GABAergic progenitors and neuroblasts in the human medial ganglionic eminence (hMGE). We show that insulin-like growth factor 1 (IGF1) and its receptor IGR1R as the top ligand-receptor pair underlying microglia-progenitor communication in the prenatal human brain. Using our newly developed neuroimmune hMGE organoids, which mimics hMGE cytoarchitecture and developmental trajectory, we demonstrate that microglia-derived IGF1 promotes progenitor proliferation and the production of GABAergic neurons. Conversely, IGF1-neutralizing antibodies and knockout human embryonic stem cells (hESC)-induced microglia (iMG) completely abolished iMG-mediated progenitor proliferation. Together, these findings reveal a previously unappreciated role of microglia-derived IGF1 in promoting proliferation of neural progenitors and the development of GABAergic neurons.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11507959 | PMC |
| http://dx.doi.org/10.1101/2024.10.19.619180 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sensory experience controls dendritic structure and behavior by distinct pathways involving degenerins.
Elife
January 2025
Department of Biology, Technion - Israel Institute of Technology, Haifa, Israel.
Dendrites are crucial for receiving information into neurons. Sensory experience affects the structure of these tree-like neurites, which, it is assumed, modifies neuronal function, yet the evidence is scarce, and the mechanisms are unknown. To study whether sensory experience affects dendritic morphology, we use the arborized nociceptor PVD neurons, under natural mechanical stimulation induced by physical contacts between individuals.
View Article and Find Full Text PDFPositive associations between mean ambient temperature and involuntary admissions to psychiatric facilities.
Eur Psychiatry
January 2025
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Background: Temperature increases in the context of climate change affect numerous mental health outcomes. One such relevant outcome is involuntary admissions as these often relate to severe (life)threatening psychiatric conditions. Due to a shortage of studies into this topic, relationships between mean ambient temperature and involuntary admissions have remained largely elusive.
View Article and Find Full Text PDFPatterns of Cerebellar-Cortical Structural Covariance Mirror Anatomical Connectivity of Sensorimotor and Cognitive Networks.
Hum Brain Mapp
January 2025
Department of Psychology, Concordia University, Montreal, Quebec, Canada.
The cortex and cerebellum are densely connected through reciprocal input/output projections that form segregated circuits. These circuits are shown to differentially connect anterior lobules of the cerebellum to sensorimotor regions, and lobules Crus I and II to prefrontal regions. This differential connectivity pattern leads to the hypothesis that individual differences in structure should be related, especially for connected regions.
View Article and Find Full Text PDFAltered Connectome Topology in Newborns at Risk for Cognitive Developmental Delay: A Cross-Etiologic Study.
Hum Brain Mapp
January 2025
Center for MR Research, University Children's Hospital Zurich, Zurich, Switzerland.
The human brain connectome is characterized by the duality of highly modular structure and efficient integration, supporting information processing. Newborns with congenital heart disease (CHD), prematurity, or spina bifida aperta (SBA) constitute a population at risk for altered brain development and developmental delay (DD). We hypothesize that, independent of etiology, alterations of connectomic organization reflect neural circuitry impairments in cognitive DD.
View Article and Find Full Text PDFPotential Adaptive Introgression From Dogs in Iberian Grey Wolves (Canis lupus).
Mol Ecol
January 2025
Estación Biológica de Doñana (EBD-CSIC), Seville, Spain.
Invading species along with increased anthropogenization may lead to hybridization events between wild species and closely related domesticates. As a consequence, wild species may carry introgressed alleles from domestic species, which is generally assumed to yield adverse effects in wild populations. The opposite evolutionary consequence, adaptive introgression, where introgressed genes are positively selected in the wild species, is possible but has rarely been documented.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!