ArticlePloS one2012
The interleukin 3 gene (IL3) contributes to human brain volume variation by regulating proliferation and survival of neural progenitors.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Genetic analysis of quantitative phenotypes in AD and MCI: imaging, cognition and biomarkers.Brain imaging and behavior · 2014Pooled it
- Pooled it
- Mast Cells in the Developing Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Context-Dependent Regulation of Microglial Metabolic and Immune States via IL-3/CD123 Signaling: Implications for Glial Crosstalk and Cognitive Impairment.Molecular neurobiology · 2026Review
- Article
- Interleukin 3 Inhibits Glutamate-Cytotoxicity in Neuroblastoma Cell Line.Neurochemical research · 2024Article
- Interleukin-3 gets a fresh start in the brain.Genes and immunity · 2023Article
- Promoting Immortalized Adipose-Derived Stem Cell Transdifferentiation and Proliferation into Neuronal-Like Cells through Consecutive 525 nm and 825 nm Photobiomodulation.Stem cells international · 2022Article
- Gut microbial dysbiosis correlates with stroke severity markers in aged rats.Frontiers in stroke · 2022Article
- Transcriptome of rhesus macaque (Macaca mulatta) exposed to total-body irradiation.Scientific reports · 2021Article
- Changes in Chemokines and Chemokine Receptors Expression in a Mouse Model of Alzheimer's Disease.International journal of biological sciences · 2019Article
- Role of the β Common (βc) Family of Cytokines in Health and Disease.Cold Spring Harbor perspectives in biology · 2018Review
- A dual role for the N-terminal domain of the IL-3 receptor in cell signalling.Nature communications · 2018Article
- Anti-colony-stimulating factor therapies for inflammatory and autoimmune diseases.Nature reviews. Drug discovery · 2016Review
- Adaptive evolution of interleukin-3 (IL3), a gene associated with brain volume variation in general human populations.Human genetics · 2016Article
- Neuronal Release of Cytokine IL-3 Triggered by Mechanosensitive Autostimulation of the P2X7 Receptor Is Neuroprotective.Frontiers in cellular neuroscience · 2016Article
- Estrogen regulation of microcephaly genes and evolution of brain sexual dimorphism in primates.BMC evolutionary biology · 2015Article
- The contribution of natural selection to present-day susceptibility to chronic inflammatory and autoimmune disease.Current opinion in immunology · 2014Review
- Coherent somatic mutation in autoimmune disease.PloS one · 2014Review
- GATA3 controls the specification of prosensory domain and neuronal survival in the mouse cochlea.Human molecular genetics · 2013Article
Corrections and comments
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Authors and funding
27 authors at 9 institutions in 3 countries.
Funding
Abstract
One of the most significant evolutionary changes underlying the highly developed cognitive abilities of humans is the greatly enlarged brain volume. In addition to being far greater than in most other species, the volume of the human brain exhibits extensive variation and distinct sexual dimorphism in the general population. However, little is known about the genetic mechanisms underlying normal variation as well as the observed sex difference in human brain volume. Here we show that interleukin-3 (IL3) is strongly associated with brain volume variation in four genetically divergent populations. We identified a sequence polymorphism (rs31480) in the IL3 promoter which alters the expression of IL3 by affecting the binding affinity of transcription factor SP1. Further analysis indicated that IL3 and its receptors are continuously expressed in the developing mouse brain, reaching highest levels at postnatal day 1-4. Furthermore, we found IL3 receptor alpha (IL3RA) was mainly expressed in neural progenitors and neurons, and IL3 could promote proliferation and survival of the neural progenitors. The expression level of IL3 thus played pivotal roles in the expansion and maintenance of the neural progenitor pool and the number of surviving neurons. Moreover, we found that IL3 activated both estrogen receptors, but estrogen didn't directly regulate the expression of IL3. Our results demonstrate that genetic variation in the IL3 promoter regulates human brain volume and reveals novel roles of IL3 in regulating brain development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.